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Cancer in 2022

In this section, you will learn:

• In the United States, the age-adjusted overall cancer death rate has been steadily declining since the 1990s, with the reductions between 1991 and 2019 translating into nearly 3.5 million cancer deaths avoided.
• In the past three years, the number of cancer survivors living in the United States increased by more than a million, reaching greater than 18 million as of January 1, 2022.
• Certain U.S. populations have not benefited equally from the advances against cancer.
• The personal burden of cancer and its economic toll both on individuals and the U.S. health care system are expected to rise in the coming decades, highlighting the urgent need for more research to accelerate the pace of progress against cancer.

Research: Driving Progress Against Cancer

Cancer: an ongoing public health challenge in the united states and worldwide, variable progress among stages at diagnosis and types of cancer, disparities in progress for certain population groups, the growing burden of cancer, the global challenge of cancer, funding cancer research: a vital investment.

Medical research is the foundation of progress against the collection of many diseases we call cancer. Research improves survival and quality of life for people around the world because it is the driving force behind every advance in cancer science and medicine and every legislative action designed to improve public health. Each breakthrough against cancer is the culmination of a complex, multifaceted process that takes long-term commitment and years of effort by individuals from all segments of the medical research community (see sidebar on The Medical Research Community: Driving Progress Together ).

The remarkable progress being made against cancers—in particular, improvements in reducing smoking rates and developments in early detection and treatment—is resulting in cancer death rates falling steadily and in a rising number of people who survive a cancer diagnosis. In fact, the age-adjusted overall cancer death rate has declined by 32 percent between 1991 and 2019 in the United States, a reduction that translates into nearly 3.5 million cancer deaths avoided ( 1 ) Siegel RL, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:7-33. [LINK NOT AVAILABLE] . Among children and adolescents with cancer, overall death rates have declined by more than half between 1970 and 2019, largely due to advances in treatment ( 1 ) Siegel RL, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:7-33. [LINK NOT AVAILABLE] . In addition, in the past three years, the number of adults and children living in the United States with a history of cancer rose by more than a million, exceeding an estimated 18 million on January 1, 2022 ( 2 ) Miller KD, et al. Cancer Treatment and Survivorship Statistics, 2022. CA Cancer J Clin 2022;0:1-28. [LINK NOT AVAILABLE] .

The steady decline in the overall cancer death rate can be attributed mainly to the unprecedented progress against lung, colorectal, breast, and prostate cancer, the four most common cancer types in the United States. In fact, during the past three decades, age-adjusted death rates from lung, female breast, and colorectal cancers have decreased by 44, 42, and 53 percent, respectively ( 3 ) Kratzer TB, et al. Progress against cancer mortality 50 years after passage of the National Cancer Act. JAMA Oncol 2022;8:156-9. [LINK NOT AVAILABLE] . Furthermore, there have been significant developments against previously intractable cancers, such as melanoma, the deadliest form of skin cancer, fueled by a range of innovative new therapeutics that have moved rapidly from the bench to the clinic and received approval by the U.S. Food and Drug Administration (FDA) (see Figure 1 ). Collectively, these advances have led to the increase in five-year relative survival rate for all cancers combined from 49 percent in the mid-1970s to nearly 70 percent from 2011 to 2017, which are the most recent data available ( 1 ) Siegel RL, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:7-33. [LINK NOT AVAILABLE] .

Among the major advances made across the clinical cancer care continuum from August 1, 2021, to July 31, 2022, are the eight new anticancer therapeutics approved for use by FDA (see Table 4 ). During this period, FDA also approved two new imaging agents to help visualize cancerous cells, several artificial intelligence-based tools to improve detection and diagnosis of cancers, and new uses for 10 previously approved anticancer therapeutics.

The research that drives progress against cancer is made possible by investments from governments, philanthropic individuals and organizations, and the private sector. In the United States, government investments in medical research are administered mostly through the 27 institutes and centers of the National Institutes of Health (NIH). The largest component of NIH is the National Cancer Institute (NCI), which is the federal government’s principal agency for cancer research and training. Medical research funded by the public sector contributes significantly to novel drug development, which is critical to saving and improving lives ( 6 ) Nayak RK, et al. Public-sector contributions to novel biologic drugs. JAMA Intern Med 2021;181:1522-5. [LINK NOT AVAILABLE] ( 7 ) Galkina Cleary E, et al. Contribution of NIH funding to new drug approvals 2010-2016. Proc Natl Acad Sci U S A 2018;115:2329-34. [LINK NOT AVAILABLE] . Federal investments in government agencies conducting research, such as FDA and the Centers for Disease Control and Prevention (CDC), are also of particular importance.

Although we have made incredible progress against cancers, this group of devastating diseases continues to be an enormous public health challenge in the United States and around the world. In the United States alone, it is predicted that 1,918,030 new cases of cancer will be diagnosed in 2022 and that 609,360 people will die from the disease ( 1 ) Siegel RL, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:7-33. [LINK NOT AVAILABLE] (see Table 1 ). These estimates do not account for the consequences of COVID-19, which has proven to have an adverse impact across the spectrum of cancer research and patient care including significant declines in cancer screening and diagnosis ( 8 ) American Association for Cancer Research. AACR Report on the Impact of COVID-19 on Cancer Research and Patient Care. Accessed: June 30, 2022.[cited 2020 Jul 15]. . In addition, data from the past two years have clearly shown the heightened risks of SARS-CoV-2 infection and severe COVID-19 among patients with cancer, albeit COVID-19-related mortality among this population has decreased over time ( 8 ) American Association for Cancer Research. AACR Report on the Impact of COVID-19 on Cancer Research and Patient Care. Accessed: June 30, 2022.[cited 2020 Jul 15]. ( 9 ) Dieci MV, et al. Clinical profile and mortality of Sars-Cov-2 infection in cancer patients across two pandemic time periods (Feb 2020-Sep 2020; Sep 2020-May 2021) in the Veneto Oncology Network: The ROVID study. Eur J Cancer 2022;167:81-91. [LINK NOT AVAILABLE] . Ongoing research will uncover the long-term effects of COVID-19 on cancer outcomes ( 10 ) National Cancer Institute. NCI COVID-19 in Cancer Patients Study (NCCAPS). Accessed: Nov 27, 2021.[cited 2020 Jul 15]. .

Progress against cancers has not been uniform for all stages of a given type of disease ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. . This issue is illustrated by the fact that the five-year relative survival rates for U.S. patients vary widely depending on the stage at diagnosis ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. . As one example, among women with breast cancer and people with colorectal cancer, those whose cancer is confined to the breast, or to the colon or rectum, have five-year relative survival rates of 99 percent and 92 percent, respectively, while those whose cancer has spread to a distant site have five-year relative survival rates of 30 percent and 16 percent, respectively ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. .

An additional challenge that we face is the uneven progress against various cancer types ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. . For example, the overall five-year relative survival rates of nearly 91 percent for women with breast cancer and 97 percent for men with prostate cancer stand in stark contrast to the overall five-year relative survival rates of 21 percent for people with liver cancer and less than 12 percent for those with pancreatic cancer ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. . While some of these differences could be attributed to early detection of breast and prostate cancers through population level screening (see sidebar on Ways to Screen for Cancer ), disparities in five-year relative survival rates hold true for patients with these four cancer types even when their diseases are diagnosed at an advanced stage. The five-year relative survival rates of greater than 30 percent for advanced-stage female breast and male prostate cancers are significantly higher than the five-year relative survival rates of less than five percent for those with advanced-stage liver or pancreatic cancer ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. .

Among children ages one to 14 years, cancer is the second-leading cause of death, and the most diagnosed cancers are leukemia and brain tumors ( 1 ) Siegel RL, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:7-33. [LINK NOT AVAILABLE] . Thanks to extraordinary advances in treatments for childhood leukemia, the age-adjusted mortality rate from the disease has almost halved in the past two decades. Unfortunately, mortality rates from childhood brain and other central nervous system tumors have essentially remained unchanged ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. .

Developing new and effective tests for early detection of more types of cancer as well as better treatment options for all cancer types and for all stages of diagnosis could help address the challenges of variable progress against different types of cancer.

Cancer health disparities are one of the most pressing public health challenges in the United States. NCI defines cancer health disparities as adverse differences in cancer such as number of new cases, number of deaths, cancer-related health complications, survivorship and quality of life after cancer treatment, screening rates, and stage at diagnosis that exist among certain population groups ( 12 ) Cancer health disparities definitions and examples. Accessed: April 22, 2022.[cited 2020 Jul 15]. (see sidebar on Which U.S. Population Groups Experience Cancer Health Disparities? ).

As outlined in the AACR Cancer Disparities Progress Report 2022, racial and ethnic minorities and other medically underserved U.S. populations shoulder a disproportionately higher burden of cancer (see sidebar on Disparate Burden of Cancer in the U.S. ) ( 13 ) American Association for Cancer Research. AACR Cancer Disparities Progress Report 2022. Accessed: June 30, 2022.[cited 2020 Jul 15]. . As one example, the U.S. Black population has long experienced cancer health disparities.

In 1990, the overall cancer death rates for Black people were 33 percent higher than for White people ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. . There has been some progress in recent years as evidenced by the narrowing of the gap in cancer death rates between the Black and White populations to 13 percent in 2019, a 60 percent decline in the disparities since 1990 ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. ( 14 ) Lawrence WR, et al. Trends in cancer mortality among black individuals in the US from 1999 to 2019. JAMA Oncol 2022. [LINK NOT AVAILABLE] . However, even in 2019, overall cancer death rates were higher among Black men and women compared to all other U.S. racial and ethnic groups ( 14 ) Lawrence WR, et al. Trends in cancer mortality among black individuals in the US from 1999 to 2019. JAMA Oncol 2022. [LINK NOT AVAILABLE] .

Sexual and gender minorities (SGM) are another U.S. population that experiences cancer health disparities. According to a new report, gay men are more likely than heterosexual men to report lifetime diagnoses of cancers, and gay men and lesbian women are more frequently unable to afford many types of health care services compared to heterosexual men and women ( 15 ) Heslin KC, et al. Sexual orientation differences in access to care and health status, behaviors, and beliefs: Findings from the National Health and Nutrition Examination Survey, National Survey of Family Growth, and National Health Interview Survey. Natl Health Stat Report 2022:1-16. [LINK NOT AVAILABLE] . Unfortunately, there are limited data on the epidemiology of cancer incidence and outcomes among SGM individuals making it difficult to evaluate the true burden of cancer in this underserved population. It is imperative that researchers collect disaggregated data by sexual orientation and gender identity, as well as within sexual minority groups (e.g., gay versus bisexual) and gender minority groups (e.g., transgender versus nonbinary) to accurately capture cancer epidemiology in these heterogeneous populations ( 13 ) American Association for Cancer Research. AACR Cancer Disparities Progress Report 2022. Accessed: June 30, 2022.[cited 2020 Jul 15]. .

Research has identified complex and interrelated factors, often referred to as the social determinants of health, including socioeconomic, cultural, behavioral, environmental, and clinical factors that contribute to cancer health disparities. It is increasingly evident that structural racism and systemic injustices cause adverse differences in social determinants of health, creating conditions that perpetuate health inequities, including cancer health disparities (see sidebar on Why Do U.S. Cancer Health Disparities Exist? ).

One of the drivers of cancer health disparities is general health of a population group. For instance, individuals with underlying health conditions, such as diabetes, or those infected with certain pathogens, such as human immunodeficiency virus (HIV), experience a greater burden of cancer (see sidebar on Cancer Burden Among People Living with HIV ). It should be noted that individuals with intersectional identities often experience multilevel barriers to optimal health care that adversely impact cancer incidence and outcomes. As one example, among individuals living with HIV, those who are from racial and ethnical minority populations may experience worse cancer health disparities ( 20 ) Elizabeth Read-Connole, et al. Basic/Translational research on Health Disparities in HIV/AIDS and cancer (Clinical trial optional). 2022. [LINK NOT AVAILABLE] . Understanding the biological drivers of cancer health disparities in marginalized populations with an underlying HIV/AIDS diagnosis is an area of active investigation ( 20 ) Elizabeth Read-Connole, et al. Basic/Translational research on Health Disparities in HIV/AIDS and cancer (Clinical trial optional). 2022. [LINK NOT AVAILABLE] .

Considering that a significant proportion of the U.S. population is affected by cancer health disparities, it is important that public health experts intensify research efforts designed to improve our understanding and mitigating of these disparities. Only with new insights obtained through innovative research, including basic science using biospecimens from diverse populations, clinical trials involving participants from all sociodemographic backgrounds, and health care delivery research, will we develop and implement interventions that may eventually eliminate cancers for all populations.

The public health challenge posed by cancer is predicted to grow considerably in the coming decades unless we develop and implement more effective strategies for cancer prevention, early detection, and treatment ( 26 ) International Agency for Research on Cancer. Global Cancer Observatory. Accessed: July 15, 2022.[cited 2020 Jul 15]. . In the United States alone, the number of new cancer cases diagnosed each year is expected to reach nearly 2.3 million by 2040 ( 26 ) International Agency for Research on Cancer. Global Cancer Observatory. Accessed: July 15, 2022.[cited 2020 Jul 15]. . This is largely because cancer is primarily a disease of aging; 80 percent of U.S. cancer diagnoses occur among those who are 55 or older; 57 percent of diagnoses occur among those 65 and older ( 1 ) Siegel RL, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:7-33. [LINK NOT AVAILABLE] , and this segment of the U.S. population is expected to grow from 54.1 million in 2019 to nearly 81 million in 2040 ( 27 ) U.S. Department of Health and Human Services. Administration for Community Living. 2020 Profile of Older Americans. Accessed: Jul 6, 2022.[cited 2020 Jul 15]. . Also contributing to the projected increase in the number of U.S. cancer cases are high rates of obesity and physical inactivity, which are both linked to some common types of cancer, and the continued use of tobacco products among certain U.S. populations.

Progress has been made toward reducing cancer incidence in the United States; new cancer cases have declined 10 percent from their peak in 1992 to 2019, the year for which the most recent data are reported ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. . However, overall cancer incidence has been rising among the U.S. adolescent and young adult (AYA) population (ages 15 to 39), which has seen nearly a 20 percent increase in cancer incidence from 2000 to 2019 ( 5 ) National Cancer Institute. Surveillance, Epidemiology, and End Results program explorer. Accessed: June 30, 2022.[cited 2020 Jul 15]. . In addition, the incidence of certain cancer types is steadily increasing, specifically among people younger than 50. As one example, many recent studies have reported an increase in the incidence of early-onset colorectal cancer among those age 49 and younger ( 28 ) Sinicrope FA. Increasing incidence of early-onset colorectal cancer. N Engl J Med 2022;386:1547-58. [LINK NOT AVAILABLE] ( 29 ) Calip GS, et al. Colorectal cancer incidence among adults younger than 50 years-understanding findings from observational studies of lower gastrointestinal endoscopy. JAMA Oncol 2022;8:981-3. [LINK NOT AVAILABLE] . The reasons behind rising cases of early-onset colorectal cancers are not completely understood but is presumed to be multifactorial, including contributions of modifiable lifestyle factors such as unhealthy diet and physical inactivity as well as factors that alter the gut microbiome such as use of antibiotics. To reduce the burden of early-onset colorectal cancer, many professional societies have modified their screening guidelines to recommend starting colorectal cancer screening at an earlier age. Additionally, researchers are evaluating new and improved strategies including genetic testing and others for prevention and early detection of colorectal cancer in the younger population ( 28 ) Sinicrope FA. Increasing incidence of early-onset colorectal cancer. N Engl J Med 2022;386:1547-58. [LINK NOT AVAILABLE] .

Beyond the United States, cancer is an ongoing global challenge (see sidebar on Global Burden of Cancer ). According to a new analysis, there were an estimated 17.2 million new cancer cases (excluding nonmelanoma skin cancer) and 10 million cancer deaths globally, in 2019 ( 30 ) Kocarnik JM, et al. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: A systematic analysis for the global burden of disease study 2019. JAMA Oncol 2022;8:420-44. [LINK NOT AVAILABLE] . The study evaluated cancer burden from 204 countries and territories as indicated by cancer-related deaths, as well as disability-adjusted life years (DALYs) and years of life lost (YLLs), which are two measures of cancer morbidity. Researchers found that among the 22 groups of diseases and injuries analyzed, cancer was second only to cardiovascular disease in the number of deaths, DALYs, and YLLs ( 30 ) Kocarnik JM, et al. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: A systematic analysis for the global burden of disease study 2019. JAMA Oncol 2022;8:420-44. [LINK NOT AVAILABLE] . The five leading causes of cancer-related morbidity among men and women combined were lung cancer, colorectal cancer, stomach cancer, breast cancer, and liver cancer.

The study also indicated that, although there were increases in the absolute numbers of both global cancer deaths and new cases from 2010 to 2019, the age-standardized mortality and incidence rates decreased by six percent and one percent, respectively ( 30 ) Kocarnik JM, et al. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: A systematic analysis for the global burden of disease study 2019. JAMA Oncol 2022;8:420-44. [LINK NOT AVAILABLE] . These trends, however, precede the setbacks in cancer care and outcomes that have been caused by the COVID-19 pandemic. Global health experts are also concerned about the consequences of the ongoing wars that have displaced populations, further destroying health care systems, disrupting social services, and increasing risk of infectious disease transmission ( 31 ) The ASCO Post Staff. War is hell. It’s also a public health disaster, especially for people with cancer. Accessed: July 6, 2022.[cited 2020 Jul 15]. . Considering the devastating impact of these global crises on the entire continuum of cancer research and patient care as well as the growth of the global population age 65 and older ( 32 ) United Nations. Ageing. Accessed: July 6, 2022.[cited 2020 Jul 15]. , researchers caution that the burden of cancer worldwide may rise significantly in the coming decades.

Another concern among global public health experts is that, while age-standardized mortality and incidence rates are declining overall, the reduction in rates appears to be driven by countries with a higher sociodemographic index (SDI)—a composite measure of the social and economic development of a country that considers income per capita, average years of education, and total fertility rate for people younger than 25. The data indicate that age-standardized cancer incidence and mortality rates are increasing in countries with lower SDI ( 33 ) Pramesh CS, et al. Priorities for cancer research in low- and middle-income countries: a global perspective. Nat Med 2022;28:649-57. [LINK NOT AVAILABLE] .

To ensure that progress against cancer is equitable worldwide, it is imperative that the global medical research community work together and share best practices to implement newer and more effective strategies that incorporate local needs and knowledge into tailored national cancer control plans. Public health experts have identified several priorities based on present and future needs of low resource countries, including reducing the burden of advanced cancers; improving access, affordability, and outcomes of treatment, utilizing value-based care; fostering implementation research; and leveraging technology to improve cancer control ( 33 ) Pramesh CS, et al. Priorities for cancer research in low- and middle-income countries: a global perspective. Nat Med 2022;28:649-57. [LINK NOT AVAILABLE] .

Cancer exerts an immense toll because of the number of lives it affects each year and through its significant economic impact. The direct medical costs of cancer care are one measure of the financial impact of cancer, and in the United States alone, they were estimated to be $183 billion in 2015, the last year for which these data are currently available; this cost is projected to increase to $246 billion by 2030 ( 1 ) Siegel RL, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:7-33. [LINK NOT AVAILABLE] . These numbers do not include the indirect costs of lost productivity due to cancer-related morbidity and mortality, which are also extremely high. Notably, cancer patients in the United States shouldered an economic burden of $21 billion in 2019 from out-of-pocket costs and other related expenses, which is nearly 3.5 times the amount of approximately $6 billion in NCI funding for cancer research in the same year ( 38 ) Yabroff KR, et al. Annual Report to the Nation on the Status of Cancer, part 2: Patient economic burden associated with cancer care. J Natl Cancer Inst 2021;113:1670-82. [LINK NOT AVAILABLE] .

With the number of cancer cases projected to increase in the coming decades, we can be certain that both the direct and indirect costs will also escalate. The rising personal and economic burden of cancer underscores the urgent need for more research so that we can accelerate the pace of progress against cancer.

Recent advances in cancer prevention, detection, and treatment, many of which are highlighted in this report, were made as a direct result of the cumulative efforts of researchers from across the spectrum of cancer science and medicine. Much of their work, as well as that of FDA—the federal regulatory agency that assures the safety and efficacy of medical devices and therapeutic advances—is supported by funds from the federal government. The consecutive increases for the NIH budget in the last seven fiscal years have helped maintain the momentum of progress (see Investments in Research Fuel a Healthier Future ). To keep up with the pace of scientific and technological innovation, it is imperative, however, that Congress continue to provide sustained, robust, and predictable increases in investments in the federal agencies that are vital for fueling progress against cancer, in particular, NIH, NCI, FDA, and CDC, in the years ahead (see AACR Call to Action ).

• A Message from AACR
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• Cancer in 2023
• Understanding the Path to Cancer Development
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• Advancing the Frontiers of Cancer Science and Medicine
• Spotlight on Immunotherapy: Pushing the Frontier of Cancer Medicine
• Perspective: Looking to the Future of Immunology
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• Envisioning the Future of Cancer Science and Medicine
• Advancing the Future of Cancer Research and Care Through Evidence-based Policies
• AACR Call to Action
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• AACR Cancer Progress Report 2023: Steering Committee

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Home > Cancer Research Catalyst > New Dimensions in Cancer Biology: Updated Hallmarks of Cancer Published

New Dimensions in Cancer Biology: Updated Hallmarks of Cancer Published

The new year brings a new chapter in the holy book of cancer biology with the publication in the AACR journal Cancer Discovery of Hallmarks of Cancer: New Dimensions , an update to the “Hallmarks of Cancer” series. The latest edition was saluted with great enthusiasm by the scientific community as the new piece of an iconic saga, with many scientists taking to Twitter to share their excitement about seeing their field of study acknowledged among the fundamentals of cancer biology. 

The original article of the seminal series was published in 2000 by Robert Weinberg, PhD, FAACR , from the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology, and Douglas Hanahan, PhD, FAACR , from EPFL, the Swiss Federal Institute of Technology in Lausanne. The authors, both cancer research pioneers, organized state-of-the-art knowledge on cancer into a logical framework that recapitulated the extraordinary complexity of the disease in a small set of fundamental traits shared by most, if not all, human cancers. In addition, they introduced the concept of “enabling characteristics,” or means that enable premalignant cells to acquire the six hallmarks of cancer. 

This landmark review soon became an essential resource for cancer researchers, with tens of thousands of citations, providing a comprehensive foundation for understanding and studying cancer biology. To account for new discoveries and progress in the field, the authors provided a first update in 2011, adding two emerging hallmarks and a new enabling characteristic. 

In “Hallmarks of Cancer: New Dimensions,” Hanahan further revisited the list, proposing one new emerging hallmark and two additional enabling characteristics.  

Read on to learn more about the hallmarks of cancer, how they were expanded over time, and the latest additions. 

The original hallmarks (2000) 

Writing about the overwhelming complexity of the scientific literature on cancer in 2000, Weinberg and Hanahan forecasted that, rather than adding more information in a chaotic fashion, research in the next quarter century would bring a conceptual shift towards a more logical approach to decipher such complexity “in terms of a small number of underlying principles.” The original “ Hallmarks of Cancer ” review was the authors’ effort and contribution to this shift, leading to the enumeration of six core “rules” that orchestrate the multistep process of the transformation of normal cells into malignant cells: 

• Self-sufficiency in growth signals . While normal cells depend on external growth signals for proliferation, cancer cells can generate most of the growth signals by themselves, greatly reducing, or eliminating, their dependence on external stimuli. A corollary to this observation was a new view of cancer as a complex tissue in which malignant cells co-opt the surrounding normal cells to provide the necessary growth signals, serving as active collaborators, rather than passive bystanders. 
• Insensitivity to growth suppressive signals . Multiple antiproliferative signals maintain the homeostasis in normal tissues, pushing cells out of the cell cycle and into a temporary quiescent state, or sending them into their terminal, post-mitotic differentiation state. Transformed cells evade these antiproliferative signals by subverting the mechanisms that control cell cycle progression—for example, by disrupting the pRb pathway, and overexpressing growth-stimulating factors such as c-myc. 
• Ability to evade programmed cell death . Apoptosis is a major anticancer barrier, as becoming immortal is another way through which cancer cells continue to expand in number. Further, the authors proposed that the redundancy in cell death mechanisms could be exploited for therapeutic purposes. 
• Enabling replicative immortality. In order for cancer to grow, malignant cells have to proliferate indefinitely. While normal cells possess a limited proliferative potential and will stop dividing at some point if cultured in vitro, cancer cells have lost that restrain mechanism, governed by telomere shortening. To become immortal, malignant cells rely on the telomerase enzyme to maintain the length of their telomeres above a critical threshold that allows them to go on dividing.  
• Sustained angiogenesis. The growing tumor tissue has increased oxygen and nutrient needs and, to keep expanding, it needs to trigger the formation of new vasculature by releasing pro-angiogenic signals. At the time the authors codified this feature, it had been established that tumors go through an “angiogenic switch” that allows them to grow from microscopic to macroscopic lesions. 
• Tissue invasion and metastasis . Metastasis is the cause of the vast majority of cancer deaths. The ability to invade, settle in, and grow in distant tissues is therefore one of the main features of cancer and relies on modifications in the cancer cell interactions with their surrounding environment through e-cadherin, integrins, and other adhesion molecules, and the production of matrix-degrading proteases. 

The acquisition of multiple mutations through the loss of one or more mechanisms designated to protecting genome integrity was presented by the authors as an enabling characteristic that allows cancer cells to reach the six “biological endpoints” illustrated above. 

Weinberg and Hanahan described the six capabilities acquired by cancer cells as the successful breaching of just as many anticancer defense mechanisms wired into our cells, and suggested these characteristics were shared by the more than 100 distinct types of cancer known at the time. Thus, the hallmarks of cancer provided a few unifying concepts toward which future cancer research could gravitate. 

“The next generation” (2011) 

In 2011, Weinberg and Hanahan published an update discussing the progress made over the preceding decade in the knowledge about the six original hallmarks. They also incorporated two emerging hallmarks: 

• Reprogramming energy metabolism . While normal cells use oxygen to process glucose and produce energy, malignant cells can switch to aerobic glycolysis even in the presence of oxygen (what is known as the Warburg effect). Though this mechanism is less efficient, it is faster and originates several intermediate precursors used by cancer cells as building blocks to make proteins, DNA, and lipids to support their fast proliferation. Other cancer cells can use lactate as their main energy source. 
• Evading immune destruction . Hanahan and Weinberg discussed evidence supporting the central role played by the immune system as a barrier to tumorigenesis, including studies in mouse models demonstrating that carcinogen-induced tumors developed and grew more rapidly in immunodeficient mice, especially if they lacked cytotoxic and helper T cells or natural killer cells, and observations that human tumors with high immune infiltration had better prognosis.  

The 2011 edition also identified tumor-promoting inflammation as a new enabling characteristic. While immune infiltrates were historically considered a sign of the immune system reacting against the tumor, at the time the second review was published, the tumor-promoting effect of certain inflammatory cells had become clear. The authors discussed how inflammation favors multiple hallmark capabilities by providing growth, survival, and proangiogenic factors, and releasing chemicals, such as reactive oxygen species, that can cause additional mutations in the nearby cancer cells.  

The review also contains a paragraph on the tumor microenvironment, which in the previous decade had become the subject of extensive research showing that, when studying the biology of a tumor, one needs to consider both the cancer cells and the microenvironment they construct around them.  

“New Dimensions:” Expanding the Frontiers of Cancer Biology (2022) 

Ten years later, Hanahan goes back to the hallmarks once more, recognizing the great progress made in the study of cancer through big data, and reaffirming the impact of the hallmarks of cancer in conceptualizing the new discoveries and “helping to distill this complexity into an increasingly logical science.” In the latest article, the two hallmarks added as emerging in 2011 were definitively incorporated as core hallmarks, as research in the past 10 years has largely confirmed the importance of metabolic reprogramming and avoiding immune destruction in cancer. In addition, Hanahan proposed an additional emerging hallmark: 

• Phenotypic plasticity and disrupted differentiation . Terminal differentiation in normal cells is associated with a permanent proliferation arrest, and increasing evidence indicates that malignant cells evade differentiation and unlock what is known as phenotypic plasticity to continue to grow. In other words, they can change their identity into something that is more inclined to proliferate. This can happen in different ways: Cells that are approaching full differentiation can de-differentiate back to a progenitor-like state; neoplastic cells originating from an undifferentiated progenitor cell can halt the differentiation process and remain in that partially differentiated, progenitor-like state; and cells that were committed to a certain differentiation phenotype can switch developmental programs, or transdifferentiate, acquiring traits that are not associated with their cell of origin. Hanahan notes that, as it is true for other hallmark capabilities, cellular plasticity is not a “novel invention” of cancer cells, but rather a malignant twist on existing mechanisms that some normal cells can activate to repair and regenerate normal tissues. 

The new article also highlights two new enabling characteristics: 

• Non-mutational epigenetic reprogramming. Global changes in the epigenetic landscape are indeed recognized as a common feature of many cancers. Reproducing what happens during normal embryogenesis and development, cancer cells can reprogram a large number or gene-regulation networks to alter gene expression and favor the acquisition of hallmark capabilities. 
• The microbiome. Our body is colonized by a vast array of microorganisms—nearly 40 trillion cells—that live in and on us. Their profound contribution to human health and disease is now appreciated. For example, researchers have found that some of these microorganisms can exert protective or deleterious effects on cancer development, progression, and response to therapy. 

The new edition acknowledged the importance of senescent cells as instrumental components of the tumor microenvironment. While in the 2000 edition the authors discussed senescence as a possible anticancer barrier, they did not rule out the possibility of it being an artifact of cell culture that did not represent a real cell phenotype in vivo. More than two decades later, the role of cellular senescence in tissue homeostasis and cancer is well recognized, and significant morphological and metabolic features associated with it have been uncovered. Research has also shown how, in certain contexts, senescent cells can stimulate tumor development and malignant progression. Therefore, Hanahan proposed that senescent cells should be included as significant components of the tumor microenvironment. 

In the concluding remarks, Hanahan explains how, while some of the hallmarks are now well validated, the newest features added as emerging hallmarks are meant to serve as “trial balloons” to stimulate debate within the cancer research community and inspire new investigations that will keep refining our understanding of cancer biology. 

On to the next decade of discoveries. 

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Cancers are a complicated disease that causes rapid multiplication and growth of specific cells of the body. It can lead to cancer or neoplasm, an unusual mass of tissues. Oncology is a medical discipline dealing with the diagnosis and management of cancer. If left untreated, it can progress into serious conditions endangering the life of the patients. Understanding disease at the cellular level can upgrade. The accuracy of disease diagnosis, management, and prevention of cancers. Additionally, a solid understanding of cancer with the assistance of disease tests from patients encourages clinical interpretations to forestall, treat and alleviate disease and related intricacies.

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Cancers , Volume 14, Issue 4 (February-2 2022) – 245 articles

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Dramatic rise in cancer in people under 50

Kira Sampson

Brigham and Women’s Hospital Communications

Altered microbiome, sleep deprivation, increase in alcohol consumption among possible culprits in 30-year global trend

A study by researchers from Brigham and Women’s Hospital reveals that the incidence of early onset cancers — including breast, colon, esophagus, kidney, liver, and pancreas — has dramatically increased around the world, with the rise beginning around 1990. In an effort to understand why many more people under 50 are being diagnosed with cancer, scientists conducted extensive analyses of available data, including information on early life exposures that might have contributed to the trend. Results are published in Nature Reviews Clinical Oncology.

“From our data, we observed something called the birth cohort effect. This effect shows that each successive group of people born at a later time — e.g., a decade later — have a higher risk of developing cancer later in life, likely due to risk factors they were exposed to at a young age,” said Shuji Ogino , a professor at Harvard Chan School and Harvard Medical School and a physician-scientist in the Department of Pathology at the Brigham. “We found that this risk is increasing with each generation. For instance, people born in 1960 experienced higher cancer risk before they turn 50 than people born in 1950, and we predict that this risk level will continue to climb in successive generations.”

Ogino worked with lead author Tomotaka Ugai and colleagues from 2000 to 2012 to analyze global data on 14 cancer types that showed increased incidence in adults before age 50. Then the team searched for available studies that examined trends of possible risk factors, including early life exposures in the general populations. Finally, the researchers examined the literature describing clinical and biological tumor characteristics of early onset cancers compared with cancers diagnosed after age 50.

“We found that this risk is increasing with each generation.” Shuji Ogino, professor, physician-scientist

In an extensive review, the team found that the early life “exposome,” which encompasses an individual’s diet, lifestyle, weight, environmental exposures, and microbiome, has changed substantially in the last several decades. They hypothesize that factors like the Western diet and lifestyle may be contributing to the rise in early onset cancer. The team acknowledged that this increased incidence of certain cancer types is, in part, due to early detection through cancer screening programs. They couldn’t precisely measure what proportion of this growing prevalence could solely be attributed to screening and early detection. However, they noted that increased incidence of many of the 14 cancer types is unlikely due to enhanced screening alone.

Possible risk factors for early onset cancer included alcohol consumption, sleep deprivation, smoking, obesity, and eating highly processed foods. Surprisingly, researchers found that while adult sleep duration hasn’t drastically changed over the several decades, children are getting far less sleep today than they were decades ago. Risk factors such as highly processed foods, sugary beverages, obesity, Type 2 diabetes, sedentary lifestyle, and alcohol consumption have all significantly increased since the 1950s.

“Among the 14 cancer types on the rise that we studied, eight were related to the digestive system. The food we eat feeds the microorganisms in our gut,” said Ugai. “Diet directly affects microbiome composition and eventually these changes can influence disease risk and outcomes.”

One limitation of this study is that researchers did not have an adequate amount of data from low- and middle-income countries to identify trends in cancer incidence over the decades. Going forward, Ogino and Ugai hope to continue this research by collecting more data and collaborating with international research institutes to better monitor global trends. They also explained the importance of conducting longitudinal cohort studies with parental consent to include young children who may be followed up for several decades.

“Without such studies, it’s difficult to identify what someone having cancer now did decades ago or when one was a child,” said Ugai. “Because of this challenge, we aim to run more longitudinal cohort studies in the future where we follow the same cohort of participants over the course of their lives, collecting health data, potentially from electronic health records, and biospecimens at set time points. This is not only more cost effective considering the many cancer types needed to be studied, but I believe it will yield us more accurate insights into cancer risk for generations to come.”

Ogino’s work is supported in part by the U.S. National Institutes of Health grants and the Cancer Research UK’s Cancer Grand Challenge Award. Ugai’s work is supported by grants from the Prevent Cancer Foundation, Japan Society for the Promotion of Science, and Mishima Kaiun Memorial Foundation.

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Top Cancer Research Advances at MSK in 2022

Wednesday, December 14, 2022

Researchers at MSK made discoveries about cancer at its most fundamental levels, increasing understanding of the disease and opening the possibility of new therapies.

Researchers at Memorial Sloan Kettering Cancer Center (MSK) continued to make meaningful strides against cancer in 2022. Laboratory studies conducted at the Sloan Kettering Institute (SKI) and across the institution contributed to the global understanding of how cancer arises, grows, and spreads — opening new possibilities for future therapies and treatments.

“To understand a complex disease like cancer, with its many types and forms, you have to investigate it at its most fundamental levels. This work spans fields including genetics, immunology, molecular biology, pharmacology, and many more,” says MSK President and CEO Selwyn M. Vickers, MD, FACS . “What I want everyone to understand is that MSK is as passionate about our research enterprise as we are about providing unparalleled patient care.”

MSK is home to more than 120 research laboratories focused on better understanding every type of cancer. This includes more than 100 labs at SKI, a dedicated experimental research arm within the larger cancer center. MSK scientists are global leaders in the field , publishing their work frequently in leading scientific and medical journals, and presenting it at top national and international conferences.

Here are some of the most exciting discoveries reported over the past year, in chronological order:

A New Type of Immunotherapy Targets Elusive Cancer Cells

Some people don’t respond to cancer treatment using chimeric antigen receptor (CAR) T cells because their cancer cells have very low levels of the targeted protein, or antigen. A team led by SKI physician-scientist Michel Sadelain, MD, PhD , developed a way to engineer highly sensitive T cells that can destroy cancer cells with low antigen levels. These redesigned T cells, called HLA-independent T cell receptor (HIT) T cells, could be effective when conventional CAR T therapies would fail. The team reported this advance in Nature Medicine on January 13, 2022.

Deep Dive Into Genetic Data Yields Metastasis Clues

Can a tumor’s DNA mutations predict whether and when the cancer will spread? A research team led by MSK computational oncologists Francisco Sanchez-Vega, PhD , and Nikolaus Schultz, PhD , analyzed genomic data from 25,000 patients with 50 different types of cancer to find out. The answer, reported February 3, 2022, in Cell , was “No”; however, the six-year investigation provides important new clues about cancer’s ability to metastasize.

A New Twist on an 80-Year-Old Biochemical Pathway

A team of SKI scientists led by cell biologist Lydia Finley, PhD , reported discovering a previously unappreciated metabolic pathway — an alternate version of the famous Krebs/tricarboxylic acid (TCA) cycle. This new version of the TCA cycle allows cells to use the carbons in nutrients to build new cell biomass rather than burn them for energy. The findings, which were reported on March 9, 2022, in Nature , have broad implications for understanding how cells adapt their metabolism to meet changing needs.

Scientists Find Potential New ‘Soldier’ for Cancer Immunotherapy

A team led by SKI immunologist Ming Li, PhD , discovered a new immune cell type that might be weaponized for immunotherapy. The new cells, which the scientists call innate-like T cells, differ in notable ways from the conventional target of many immunotherapies — the cytotoxic (aka “killer”) T cells. The discovery, reported in the April 20, 2022, issue of Nature , raises hopes of narrowing the gap between people who respond to immunotherapy and those who do not.

A Sensor Sniffs for Cancer, Using Artificial Intelligence

MSK researchers, led by Kravis WiSE postdoctoral fellow Mijin Kim, PhD , and SKI biomedical engineer Daniel Heller, PhD , developed an AI-assisted nanosensor that can detect ovarian cancer signals in the blood. Once validated, the test could potentially aid early detection of ovarian cancer, which is urgently needed. The scientists reported the research in the May 12, 2022, issue of Nature Biomedical Engineering .

Finding a New — and Common — Subtype of Prostate Cancer

Scientists at MSK and Weill Cornell Cancer Center identified a previously uncharacterized subtype of hormone-resistant prostate cancer that accounts for about 30% of all cases. The finding, reported in Science on May 27, 2022, could pave the way for targeted therapies for people with this subtype of prostate cancer. The team, led by MSK physician-scientist Yu Chen MD, PhD , a member of the Human Oncology and Pathogenesis Program , used organoids and patient-derived xenografts (cells from tumors implanted into immunodeficient mice) to identify the subtype, which they call stem cell-like (SCL), because some of the genes that are turned on in the cells are reminiscent of those in stem cells.

A Natural Defense Against Viruses Can Lead to Cancer Cell Mutations

APOBEC3 enzymes normally play a role in defending the body from viruses by disrupting their DNA. A research team led by SKI molecular biologist John Maciejowski, PhD , found strong evidence that the enzymes also play a role in causing cancer-related mutations. The discovery was reported in Nature on July 20, 2022.

A Surprising Way for Pancreatic Cancer to Spread

Schwann cells wrap around nerves like insulation around an electric cable. The laboratory of MSK physician-scientist Richard J. Wong, MD, FACS , discovered that Schwann cells organize into tracks, through which pancreatic cancer cells can travel. In addition to blood vessels and the lymphatic system, the Schwann cells represent a third avenue for cancer to spread from the pancreas. As the researchers reported in the August 3, 2022, issue of Cancer Discovery , a protein called c-Jun is key to this process.

SKI Scientists Solve 30-Year-Old Mystery About p53 Protein — Dubbed ‘Guardian of the Genome’

More than half of all cancers have mutations in a gene called p53 , often called the “guardian of the genome.” Cells without working p53 are unable to properly repair damaged DNA, leading to a buildup of mutations. A study led by SKI cancer biologist Scott Lowe, PhD , found that loss of p53 is followed by an orderly progression of predictable genetic changes — not genetic chaos, as previously believed. The researchers, who reported this finding in the August 17, 2022, issue of Nature , say that knowing that there are “rules” to the genetic evolution of tumors suggests a different way of thinking about treating them.

MSK Researchers Discover How Cancer Cells Change Identity To Escape Therapies

Some prostate tumor cells completely change their identity to resist drugs. This transformation, known as lineage plasticity, allows cancer cells to convert to a different cell type. Research done in laboratory models and led by physician-scientist Charles Sawyers, MD , and Sloan Kettering Institute computational biologist Dana Pe’er, PhD , identified signaling pathways that, if blocked, resensitize cells to therapy — potentially opening the door to new clinical approaches. The findings are reported in the September 2, 2022, issue of Science .

New MACHETE Technique Slices Into Cancer Genome To Study Copy Number Alterations

MACHETE, a new CRISPR-based technique to study large-scale genetic deletions efficiently in laboratory models, shed new light on a genetic change that contributes to about 15% of all cancers. The finding, reported on December 7, 2022, in Nature Cancer by postdoctoral fellows Kaloyan Tsanov, PhD , and Francisco “Pancho” Barriga, PhD , in the laboratory of SKI cancer biologist Scott Lowe, PhD , might help identify patients likely to respond to immunotherapies.

Shedding Light on Ovarian Cancer Resistance to Immunotherapy

Ovarian cancers have been stubbornly resistant to immunotherapy compared with many other cancers. A study led by computational oncologist Sohrab Shah, PhD , and medical oncologist Dmitriy Zamarin, MD, PhD, found that ovarian cancer is even more complex than previously understood. The teams discovered there are profound differences among tumors of the same high-grade serous subtype and between the different tumor sites within the same patient. They also learned that ovarian tumors develop new mutations to hide from the immune system as they spread. The research, reported on December 14, 2022, in Nature , reveals mechanisms driving resistance, providing an opportunity to find better ways to improve treatments.

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Cancer Facts & Figures 2022

Cancer Facts & Figures 2022 is an educational companion for Cancer Statistics 2022, a scientific paper published in the American Cancer Society journal, CA: A Cancer Journal for Clinicians . The Facts & Figures annual report provides:

• Estimated numbers of new cancer cases and deaths in 2022 (In 2022, there will be an estimated 1.9 million new cancer cases diagnosed and 609,360 cancer deaths in the United States.)
• Current cancer incidence, mortality, and survival statistics
• Information on cancer symptoms, risk factors, early detection, and treatment

Also see this news story:  Risk of Dying from Cancer Continues to Drop at an Accelerated Pace

Please note: The projected numbers of new cancer cases and deaths in 2022 should not be compared with previous years to track cancer trends because they are model-based and vary from year to year for reasons other than changes in cancer occurrence. Age-standardized incidence and death rates should be used to measure cancer trends. In addition, estimates for 2022 do not reflect the impact of the COVID-19 pandemic because they are based on incidence and mortality data reported through 2018 and 2019, respectively.

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If you smoke and have been diagnosed with cancer in the last 24 months, you may be eligible to participate in a research study that will test a smartphone app to help you quit smoking. 

See if the trial is for you or someone you love:  Quit2heal.org

2022 Special Section: Cancer in the American Indian and Alaska Native Population

This year's  special section  reviews cancer occurrence in the American Indian and Alaska Native (AIAN) population, including the prevalence of cancer risk factors and screening. It highlights racial and geographic disparities and is intended to inform anyone interested in learning more about cancer in American Indians and Alaska Natives, including policy makers, researchers, clinicians, cancer control advocates, patients, and caregivers.

2022 Supplemental Data

This supplemental data set can be used as a resource for cancer control planning at the state level, as well as to address questions from the media or American Cancer Society (ACS) constituents. ACS Regions are encouraged to share this information with staff and volunteers, and to use it with state and local officials, reporters, and other public health and advocacy groups in local communities.

The estimated numbers of new cancer cases and deaths by state and the lifetime probabilities of developing or dying from cancer are also available in an interactive format from the  Cancer Statistics Center .

• Estimated Number of New Cases for the Four Major Cancers by Sex & Age Group, 2022 (PDF)
• Estimated Number of Deaths for the Four Major Cancers by Sex & Age Group, 2022 (PDF)
• Estimated Number of New Cases & Deaths by State for 21 Cancer Sites, 2022 (PDF)
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Most Requested Tables and Figures

The most requested tables and figures from Cancer Facts & Figures 2022 have been assembled in an electronic format (PDF) to make it easy for you to use them. Please note that all graphic material should credit the "American Cancer Society, Cancer Facts & Figures 2022.”

• Trends in Age-adjusted Cancer Death Rates by Site, Males, US, 1930-2019 (PDF)
• Trends in Age-adjusted Cancer Death Rates by Site, Females, US, 1930-2019 (PDF)
• Estimated Number of New Cancer Cases and Deaths by Sex, US, 2022 (PDF)
• Estimated Number of New Cases for Selected Cancers by State, US, 2022 (PDF)
• Estimated Number of Deaths for Selected Cancers by State, US, 2022 (PDF)
• Leading Sites of New Cancer Cases and Deaths - 2022 Estimates (PDF)
• Probability of Developing Invasive Cancer During Selected Age Intervals by Sex, US, 2016-2018 (PDF)
• Incidence and Mortality Rates for Selected Cancers by Race and Ethnicity, US, 2014-2019 (PDF)

Cancer Statistics 2022 Slide Presentation

Use the button to download a slide presentation of an overview of current cancer statistics in the US.  

Cancer Statistics Center

Visit the American Cancer Society’s Cancer Statistics Center to explore, interact with, and share cancer statistics. Create custom downloadable maps, graphs, and charts, and export data to Excel.

ACS Research in Plain Words

Our Research Highlights overview some of our most game-changing research from American Cancer Society (ACS) staff scientists and from medical schools and universities across the United States that we help support with research grants.

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Our most important cancer research stories of 2022

14 December 2022

Stopping cancer from spreading  

Cancer is at its most dangerous when it spreads through the body. This is called metastasis.   

Until this year, we didn’t really understand how the process worked, which limited what we could do to stop it.  

But, in October, scientists at our Cambridge Institute identified a protein that regulates metastasis, completely changing our understanding of how cancer spreads.  

The protein, known as NALCN (nal-kan), isn’t unique to cancer, either. It turns out that cancer cells manipulate it so they can exploit a process that also occurs in healthy tissues. They may even be turning one of the body’s repair mechanisms to their own destructive ends.  

By using drugs to turn NALCN back on in cancer cells, researchers might be able to stop them from spreading through the body, effectively preventing the main cause of cancer death.   

Group leader Professor Richard Gilbertson called it one of the most important findings to come out of his lab in 30 years of research.  

“If you could stop metastasis,” he told us, “or significantly suppress it, you’re getting towards managing cancer for the long term, and that’s the Holy Grail.”  

• Find out more about the revolution in our understanding of metastasis .

Sparing people from treatments they don’t need  

Every cancer is different. It’s hard to believe, but some won’t even cause noticeable health problems.

Prostate cancers are a good example. Many grow too slowly to make any difference to the length or quality of a person’s life.  

And if a cancer isn ‘t going to have any meaningful health impacts, we don’t need to treat it . That means sparing people from drugs and procedures that can cause their own harmful side effects.

To do that, though, we need a way to tell the difference between aggressive and slow-growing cancers. This year, some of our funded researchers may have found one.

Their approach involves an advanced type of MRI, which is commonly used by doctors to see what’s going on inside the body. The team used it to accurately identify which tumours were ‘clinically significant’ and needed treatment, and which were ‘indolent’ and only needed to be observed over time.

The next step is to trial the technique in a larger group of patients. We’re funding that work, too.

“In the future this technique could help guide doctors with their treatment decisions,” said Professor Ferdia Gallagher, one of the leaders of the study, “ensuring patients undergo immediate treatment if needed, or that their cancer is monitored closely when not on treatment.”  

• Learn how the technique works.

Keeping up the pressure on lung cancer  

This year we announced TRACERx EVO, the next phase of our flagship lung cancer study.   

TRACERx is already the largest and most detailed lung cancer study of its kind. Here are just a few highlights:  

• TRACERx has taught us how to predict whether lung cancer will return after surgery and guided the use of extra therapies that can stop that happening;  
• It’s revealed some of the tricks tumour cells use to protect themselves from the immune system;    
• And it’s even shown how air pollution can cause inflammation in the lungs that can lead to lung cancer, fundamentally changing how we view the disease in people who have never smoked .  

“It’s a miracle.” Terry was diagnosed with lung cancer in 1989. Following treatment, Terry was told he was in remission, and has been a keen supporter of our work ever since. 1/2 pic.twitter.com/1iUrtza83g — Cancer Research UK (@CR_UK) November 28, 2022

But now we want to go even further. The TRACERx EVO team, which is made up of experts from across Europe and North America, will study lung cancer from its earliest to its most advanced stages to improve how we prevent, diagnose and treat it.   

In the first place, that means looking more closely at how the disease starts in people who don’t smoke. The team will also follow its progression, considering how the environment around tumours affects how the disease develops. And they’ll study cancer cachexia (kak-ex-ee-a) – the wasting syndrome that leads to severe weight loss, weakness and fatigue in 80% of people with advanced cancers.  

Today, cachexia is still poorly understood, but TRACERx has already shown just what we can find out when we combine commitment and funding with expertise and attention. We’ll keep you updated on everything that happens in the next phase of the study.  

• Delve deeper into TRACERx EVO .

Finding surprising ways to tackle drug resistance  

Sometimes, our research leads in some unexpected directions. Sometimes, they involve Viagra.  

It’s not what it sounds like. Or not entirely. This year, a team we part-funded showed that the same properties that make Viagra an effective treatment for erectile dysfunction can actually help strip away the defence systems used by some cancers. That means it could be used to make hard-to-treat tumours more sensitive to chemotherapy.  

The researchers found that chemotherapy-resistant tumours in mice shrunk more when they were treated with erectile dysfunction drugs and chemotherapy than with chemotherapy alone. That bodes well for people – we already know that drugs like Viagra are safe and well-tolerated.  

And that’s not the only exciting advance we made against treatment-resistant cancers in 2022. Another one of our research teams found a molecule in some cancers that makes targeted therapies called PARP inhibitors less effective against them.   

That molecule can be blocked with another pre-existing drug: disulfiram, which is currently used to help people cope with alcohol addiction.  

These findings show why our commitment to basic research into how cancer works is so important. Sometimes a new drug isn’t the best solution. Looking more closely at cancer can show that, in the right combinations, the tools we already have might be much more effective. And we can start using them much sooner, too.  

• Discover how researchers brought erectile dysfunction drugs to cancer treatment .  
• See how we’re working to make targeted treatments more effective .  

Taking on cancer’s biggest challenges  

Throughout 2022, the Cancer Grand Challenges initiative, which we co-founded with the US National Cancer Institute, has continued to make some of the world’s best science possible.  

For the third funding round, we gave a total of £80m to 4 teams with the vision and expertise to solve some of the deepest and most important mysteries around cancer. They’re bringing new thinking and unparalleled track records to big questions like why the disease develops in the first place and how it evolves to escape the immune system and resist treatment.  

In fact, one of our newly funded researchers, Professor Carolyn Bertozzi, even won this year’s Nobel Prize in Chemistry . She’s part of the NexTGen team, using her knowledge to help develop a gentler and more effective way to treat solid tumours in children.  

That’s not all. In December, one of the first round teams, IMAXT , launched an entirely new way to study and understand tumours. Their virtual reality cancer lab and tumour modelling technology could give scientists a more complete and integrated understanding of cancer than ever before , helping them to develop new ways to diagnose and treat it  

• Read how IMAXT is using video games to improve cancer research
• Take a closer look at the latest grand challenges  

Paying tribute to the people who make this possible  

All of this is thanks to our incredible supporters. the people that give their time, money, effort and energy to help beat cancer sooner .    

This year we lost Dame Deborah James – a deputy headteacher, who, after being diagnosed with stage 4 bowel cancer in December 2016, chose to share her story with the world. To raise awareness and challenge taboos, she became Bowelbabe, a newspaper columnist, podcaster, bestselling author and campaigner like no other. As far as attitudes to cancer are concerned, the world hasn’t been quite the same since.  

In May, with her health declining, Deborah said there was one more thing she wanted to do before she died – raise as much money and awareness as possible. She launched The Bowelbabe Fund for Cancer Research UK and set a target of raising £250,000. The total today is over £7,500,000 – more than 30 times as much. It’s a true testament to the number of lives she touched.

She worked tirelessly to support @CR_UK and other charities she was passionate about. She loved to be amongst people, working the room and making the most of every occasion. pic.twitter.com/WCTzuXH4HG — Michelle Mitchell (@Michelle_CRUK) June 29, 2022

“Deborah did whatever she could to fundraise, challenge taboos, and raise awareness of cancer – with honesty, compassion and humour,” said Michelle Mitchell, our chief executive. “She was an inspiration to so many people, and her impact will be felt for years to come.”

Dame Deborah James was one of a kind. And, in another way, she was no different from anyone else.   

1 in 2 of us will be diagnosed with cancer in our lifetime. Deborah’s brilliance and bravery is mirrored in every single person who is confronted by that news. Our work is about keeping their light in the world.  

• Why do personal stories make such a difference?  

Thank you for all your support. This is only a glimpse at the incredible work your generosity has made possible. Stay tuned next year to see more.  

Merry Christmas and a Happy New Year from Cancer Research UK.  

Thank you for the wonderful update. Was discharged from my consultant after uterine cancer a year ago following surgery.

When I read this email I cried a lot because you are discovering things that could have helped four people in our village community who have died with cancer in the last three months. I know your discoveries will help people in the future and that is a great blessing.

Very promising, but the fact is we are behind several other countries in respect of death rates – Why ? I assumed a global assault on this vile disease with data shared.

Thanks for your comment.

International differences in how likely people are to survive cancer can be the result of a variety of factors, from late-stage diagnosis to patients not having access to the most effective treatment.

The International Cancer Benchmarking Partnership (ICBP) has been reporting international variation in cancer survival for over 10 years, giving us insight into how the nations of the UK compare internationally.

You can read about their most recent research, which found a link between cancer policy consistency over time and cancer survival here . Their previous research has also shown that more cancers are being diagnosed through emergency routes in the UK than in comparable, high-income countries like Australia and Canada. You can read about that here .

However, cancer survival is improving overall in the UK and has doubled in the last 40 years , though this varies between cancer types.

I hope that helps, Jacob, Cancer Research UK

Fantastic enlightening update. My darling husband died in March 2022 from bowel cancer and it’s wonderful to see the work that is continuing to fight back at this dreadful disease.

As the wife of a husband who has malignant melanoma, I am moved to tears by the courage & stories of so many people with life threatening disease. My husband was diagnosed in 1998 & without his immunotherapy medication would not be alive today.

Wonderful update and insights behind the pioneering research in cancer right now.

A fantastic update and insight to the progress scientists are making.

I think the tireless research that you do, and the new discoveries are amazing ! I would like to increase my monthly subscription / contribution – please contact me?!

We’re so pleased you’d like to increase your monthly donation. You can do so by filling in the form here: https://www.cancerresearchuk.org/get-involved/donate/request-increase

Thank you so much for your continued support. We couldn’t do any of our work without donations from people like you.

Happy New Year! Jacob, Cancer Research UK

brilliant work eventually cancer might be defeated through your research

This is extremely encouraging! I have tremendous admiration for the dedicated researchers and for the wonderful fundraisers. Thank you so much. 👏👏

Brilliant work CRUK. It brings us cancer patients so much hope to see these amazing discoveries happen. Looking forward to your work in 2023 and hopefully advance these discoveries to the clinic

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Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches

Mamello sekhoacha.

1 Department of Pharmacology, University of the Free State, Bloemfontein 9300, South Africa

Keamogetswe Riet

2 Department of Health Sciences, Central University of Technology, Bloemfontein 9300, South Africa

Paballo Motloung

Lemohang gumenku, ayodeji adegoke.

3 Cancer Research and Molecular Biology Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan 200005, Nigeria

Samson Mashele

Associated data.

Information was available in the public domain. Databases have been provided in Section 2 .

Simple Summary

Prostate cancer affects men of all racial and ethnic groups and leads to higher rates of mortality in those belonging to a lower socioeconomic status due to late detection of the disease. There is growing evidence that suggests the contribution of an individual’s genetic profile to prostate cancer. Currently used prostate cancer treatments have serious adverse effects; therefore, new research is focusing on alternative treatment options such as the use of genetic biomarkers for targeted gene therapy, nanotechnology for controlled targeted treatment, and further exploring medicinal plants for new anticancer agents. In this review, we describe the recent advances in prostate cancer research.

Prostate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in men globally. Patients affected with prostate cancer present with either a localized or advanced disease. In this review, we aim to provide a holistic overview of prostate cancer, including the diagnosis of the disease, mutations leading to the onset and progression of the disease, and treatment options. Prostate cancer diagnoses include a digital rectal examination, prostate-specific antigen analysis, and prostate biopsies. Mutations in certain genes are linked to the onset, progression, and metastasis of the cancer. Treatment for localized prostate cancer encompasses active surveillance, ablative radiotherapy, and radical prostatectomy. Men who relapse or present metastatic prostate cancer receive androgen deprivation therapy (ADT), salvage radiotherapy, and chemotherapy. Currently, available treatment options are more effective when used as combination therapy; however, despite available treatment options, prostate cancer remains to be incurable. There has been ongoing research on finding and identifying other treatment approaches such as the use of traditional medicine, the application of nanotechnologies, and gene therapy to combat prostate cancer, drug resistance, as well as to reduce the adverse effects that come with current treatment options. In this article, we summarize the genes involved in prostate cancer, available treatment options, and current research on alternative treatment options.

1. Introduction

Prostate cancer affects middle-aged men between the ages of 45 and 60 and is the highest cause of cancer-associated mortalities in Western countries [ 1 ]. Many men with prostate cancer are diagnosed by prostate biopsy and analysis, prostate-specific antigen (PSA) testing, digital rectal examination, magnetic resonance imaging (MRI), or health screening. The risk factors related to prostate cancer include family risk, ethnicity, age, obesity, and other environmental factors. Prostate cancer is a heterogeneous disease both on the basis of epidemiology and genetics. The interplay among genetics, environmental influences, and social influences causes race-specific prostate cancer survival rate estimates to decrease, and thus, results in differences observed in the epidemiology of prostate cancer in different countries [ 2 ]. There is documented proof of a genetic contribution to prostate cancer. Hereditary prostate cancer and a genetic component predisposition to prostate cancer have been studied for years. One of the most predisposing genetic risk factors for prostate cancer is family inheritance. Twin studies and epidemiological studies have both proven the role of hereditary prostate cancer [ 3 ]. Many researchers have looked into the possible role of genetic variation in androgen biosynthesis and metabolism, as well as the role of androgens [ 4 , 5 ]. Genomics research has identified molecular processes that result in certain cancer developments, such as chromosomal rearrangements [ 2 ].

In general, gene mutations are a prevalent cause of cancer. Candidate genes for prostate cancer predisposition are genes that partake in the androgen pathway and metabolism of testosterone. The development of prostate epithelium and prostate cancer cells relies on the androgen receptor signaling pathway and testosterone [ 6 ]. The identification of cancer biomarkers and targeting of specific genetic mutations can be used for targeted treatment of prostate cancer. Biomarkers that can be used for targeted treatment are DNA tumor biomarkers, DNA biomarkers, and general biomarkers [ 7 ].

Prostate cancer can either be classified as androgen sensitive or androgen insensitive, which is an indicator of testosterone stimulation and the possible treatment option [ 8 ]. Treatment options available for prostate cancer are active surveillance, chemotherapy, radiation therapy, hormonal therapy, surgery, and cryotherapy. Treatment options delivered to a patient depend on the nature of the tumor, PSA level, grade and stage, and possible recurrence. For example, radical prostatectomy, a surgical option that involves the removal of the prostate and nearby tissues, is used in conjunction with radiation therapy for the treatment of low-risk prostate cancer [ 9 ]. For treating cancers that have spread beyond the prostate and have reoccurred, androgen-deprivation therapy, also called hormonal therapy, is recommended [ 1 ]. Each treatment is associated with severe side effects such as toxicity and reduced white and red blood cell counts, which lead to fatigue, hair loss, peripheral neuropathy, erectile incontinence and dysfunction, metastasis, and lastly, developing resistance to the initial treatment. Available treatment options are expensive and pose severe side effects. The discovery of new cost-effective chemotherapeutic agents with little or no side effects and higher efficacy is necessary [ 3 ]. In this review, we provide a holistic overview of prostate cancer, including the diagnosis of the disease, genes and mutations leading to the onset and progression of the disease, treatment options, and alternative treatment options.

2. Materials and Methods

In order to carry out the current review, in 2020, our team began to collect information and carry out a comprehensive search from different databases, i.e., Google Scholar, Pubmed, Springer, Elsevier ScienceDirect, and Web of Science, for studies published from 2010 to 2022, and older studies published as early as 2000 were included in this paper due to relevancy. The articles selected only utilized English texts, and searches were carried out for the following keywords and headings: ”prostate cancer”, ”prostate cancer genetics”, ”prostate cancer diagnosis and treatment”, ’ cancer statistics”, ”the prostate”, ”medicinal plants in prostate cancer treatment”, “traditional medicine”, “alternative therapy for prostate cancer”, ”nanomedicine in prostate cancer”, ”next generation sequencing”, “bioactive compounds in prostate cancer”, and ”drug repurposing in cancer”. Duplicate papers were eliminated, the data were screened, irrelevant works were factored out, and then full-text documents were screened. The inclusion criteria included several factors which involved original articles or review papers. The criteria for exclusion included articles with inadequate and irrelevant information and those without access to full text articles.

2.1. Epidemiology of Prostate Cancer

2.1.1. global scale.

Prostate cancer is one of the most common malignancies in men worldwide [ 10 ]. In 2018, GLOBOCAN reported approximately 1,276,106 new cases of prostate cancer resulting in about 358,989 deaths worldwide, with a higher prevalence in developed countries. On average, 190,000 new prostate cancer cases arise each year, with about 80,000 deaths occurring annually around the world [ 11 ]. The worldwide incidence of prostate cancer differs among various geographical regions and ethnic groups. Black men have the most reported incidence rates of prostate cancer in the world [ 12 ]. The incidence rates of Black Americans are approximately 60% higher than those of white men in America. The highest recorded incidence rates of prostate cancer are seen in developed countries where there is prostate cancer awareness and where prostate-specific antigen (PSA) testing is a prevalent screening practice [ 13 ]. The GLOBOCAN reports of PSA tests indicated high incidence rates in Australasia (111.6 per 100,000) and the USA (97.2 per 100,000) in the year 2012 [ 14 ]. Globally, prostate cancer is predicted to increase to approximately 1.7 million new cases and 499,000 deaths by the year 2030 because of the exponentially growing population and the large population of men who will be 65 years and older [ 15 ].

2.1.2. Local Scale

Little is known about prostate cancer in African countries. Prostate cancer screening using the PSA test or digital rectal examination is not a well-established practice in Africa. There is a higher incidence rate of prostate cancer among men in Southern Africa as compared with Northern Africa [ 16 ]. In South Africa, prostate cancer is one of the most diagnosed cancers in men across the country. As recorded by the South African National Cancer Registry, the incidence rate of prostate cancer in 2007 was 29.4 per 100,000 men. In 2012, the incidence increased to 67.9 per 100,000 men [ 15 ].

2.2. Screening and Diagnosis of Prostate Cancer

Prostate cancer diagnoses at mature stages of the disease and failure of therapy are the main factors leading to an increased mortality rate. There is no single, specific test for prostate cancer; however, it has conventionally been diagnosed by a digital rectal examination (DRE), where a gloved finger is inserted into the patient’s rectum to assess the size of the prostate gland and any abnormalities. However, the prostate-specific antigen (PSA) test remains to be the keystone for prostate cancer screening [ 17 ]. PSA is a glycoprotein secreted by the epithelial cells of the prostate gland. It is usually found in semen, but can also be found in the bloodstream [ 18 ]. During PSA testing, blood samples are taken to test the level of PSA. Then, the blood samples are analyzed at a PSA cut-off point of 4 ng/mL. PSA levels above 4 ng/mL suggest that the patient needs further testing [ 19 ]. Patients with PSA levels between 4 ng/mL and 10 ng/mL have an approximately one in four chance of having prostate cancer. If the PSA is more than 10 ng/mL the possibility of having prostate cancer is over 50% [ 20 ]. PSA is prostate gland specific and not prostate cancer specific; therefore, prostate-specific antigen levels can indicate benign pathologies such as benign prostatic hyperplasia (BPH) and prostatitis and not prostate cancer, and men who do not have prostate cancer have also been reported to have elevated PSA levels. A prostate tissue biopsy is usually performed to confirm the presence of cancer [ 21 ].

A biopsy is a medical procedure in which a thin hollow needle is used to collect small tissue samples from the prostate gland to be observed under a microscope. The biopsy can be performed through the skin between the anus and scrotum or through the rectal wall (known as a transrectal biopsy) [ 22 ]. During a biopsy, the prostate gland is usually located with devices such as magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS). An MRI scanner creates detailed images of body tissue using a strong magnetic field and radio waves [ 23 ]. MRI positive results can be used for specifically targeting abnormal areas of the prostate gland during a biopsy [ 24 ]. A multiparametric MRI can also be a triage test performed without a biopsy if the results were negative for DRE, PSA test, and MRI. A TRUS is a small probe that is deposited into the rectum of a patient. The probe emits sound waves that go through the prostate gland and produce echoes. The probe then recognizes and reads the echoes, and a computer system turns them into a black and white image of the organ [ 25 ].

Biopsy analysis is one of the most reliable methods of prostate cancer diagnosis. Tissue samples of a biopsy are studied and analyzed in the laboratory using a microscope. The cells can also be analyzed to determine how quickly cancer will spread. The biopsy results are usually reported as follows:

• Negative for prostate cancer, there were no cancer cells detected in the biopsy samples.
• Positive for prostate cancer, there were cancer cells detected in the biopsy samples.
• Suspicious, abnormal cells present, but may not be cancer cells [ 26 ].

However, artificial intelligence (AI) and machine learning algorithms have recently advanced, resulting in new classifications for prostate cancer. In recent years, the availability of novel molecular markers, as well as the introduction of advanced imaging techniques such as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography (PSMA-PET) scans have shifted the paradigm of prostate cancer screening, diagnosis, and treatment to a more individualized approach [ 27 ]. According to the most recent guidelines, any man at risk of prostate cancer should have an MRI of the prostate performed before obtaining a prostate biopsy [ 28 ]. This serves to minimize complications such as lower urinary tract symptoms, hematuria, and temporary erectile dysfunction. Furthermore, the number of biopsy cores obtained is linked to a higher risk of complications such as rectal bleeding, hematospermia, bleeding problems, and acute urine retention [ 29 ]. Therefore, radiomics can help with prostate volume selection and segmentation; prostate cancer (PCa) screening, detection, and classification; and risk stratification, treatment, and prognosis ( Table 1 ).

Benefits and drawbacks of radiogenomics as compared with actual prostate cancer peril stratification management [ 30 ].

2.3. Prostate Cancer and Genetics

Genetic inheritance.

Close family lineage is the primary risk factor for prostate cancer. Men with close relatives diagnosed with prostate cancer are at a 50% risk of developing cancer as compared with men with no family history of prostate cancer [ 26 ]. First-degree relatives with successive generations of diagnosed prostate cancer usually have early onset prostate cancer [ 31 ]. Epidemiologic studies have shown the inheritance of prostate cancer susceptibility genes. Analyses of case-control, twin, and family studies have concluded that prostate cancer risk may be a result of heritable factors. Research has shown specific gene mutations in hereditary prostate cancer and has reported that patients with these mutations have an increased risk of the disease [ 4 ]. In the genetic evaluation of inheritance, scientists use multigene sequencing of men diagnosed with prostate cancer, as well as men at high risk of developing cancer. About 5.5% of these men had detectable mutations in DNA repair genes such as ATM , BRCA1 , and BRCA2 genes. African men have certain genetic mutations that predispose them to prostate cancer; therefore, race and environmental conditions such as migration and food diets are considered to be contributing factors [ 21 ].

Cancer occurs because of changes in the DNA sequence due to mutations such as point mutations, single nucleotide polymorphisms (SNPs), and somatic copy number alterations (SCNAs) [ 31 ]. Mutations can cause prostate cells to become cancerous by turning off tumor suppressor genes and turning on oncogenes [ 32 ]. This often leads to uncontrolled cell division. Mutations in genes can be passed on from generation to generation or be acquired by an individual. Acquired mutations usually occur during DNA replication in the nucleus [ 33 ]. The common genes used as biomarkers for prostate cancer are BRCA genes, HOX genes, the ATM gene, RNase L (HPC1, lq22), MSR1 (8p), and ELAC2/HPC2 (17p11). Table 2 shows most of the genes used as biomarkers for prostate cancer.

Prostate cancer genes used as biomarkers for the disease.

Biomarkers show the advantages of being used for diagnostic procedures, staging, assessing the aggressiveness of the disease, and evaluating the therapeutic process. Multiple advances have been achieved through profiling technologies, including novel biomarkers that guide diagnosis and precision medicine. Modern biological markers, such as the prostate health index (PHI), the TMPRSS2-ERG fusion gene, 4K tests, and PCA3, have proven to increase PSA specificity and sensitivity, resulting in patients avoiding biopsies and reducing over diagnosis [ 76 ]. Table 3 below shows different diagnostic biomarkers and their different tests and categories.

Examples of other diagnostic biomarkers classified as serum-based, urine-based, and tissue-based biomarkers used for prostate cancer [ 77 ].

Figure 1 depicts the developmental stages of prostate cancer [ 78 ].

A schematic depicting the development of prostate cancer. The stages of the cancer onset and progression are indicated by the molecular processes, genes, and signaling pathways which are important in different stages of cancer. The first sign of prostate cancer is an inflammation of the prostate gland as a result of uncontrollable cell division. This uncontrollable cell division is caused by mutations that arise due to damaged DNA. At a chromosomal level, the initiation of prostate cancer begins with the shortening of telomerase at the end of the chromosome. Oxidative stress from prostate gland inflammation can shorten prostatic telomeres [ 78 ]. Research on the Nkx3.1 homeobox gene has shown the impact of the gene on the prostate cancer initiation phase in mice. No tumor suppressor gene has been solely given a role in prostate cancer initiation or progression. However, several genes such as MYC , PTEN , NKX3.1 ., and TMPRSS2-ERG gene fusions are implicated in prostate cancer initiation. TMPRSS2-ERG gene fusions are responsible for the main molecular subtype of prostate cancer. The gene fusion activates the ERG oncogenic pathway, which contributes to the development of the disease. Metastasis of prostate cancer is conserved by the reactivation of pathways involved in cell division, which results in uncontrolled cell division and cell proliferation, leading to metastasis of the cancer [ 79 ]. Gene expression profiling results have indicated an overexpression in EZH2 mRNA and proteins present in metastatic prostate cancer. Due to the functions of EZH2 involving apoptosis and proliferation, EZH2 is a novel target for prostate cancer [ 80 ].

2.4. Precision Medicine for Prostate Cancer

Precision medicine is an emerging field that represents an alternative method, for some men with advanced cancer, to find gene-specific treatment for prostate cancer. It uses genetics as well as environmental biomarkers to determine diagnoses, prognosis therapeutic options for patients, and accurate dosing. Precision medicine classifies diseases using genome sequencing to identify patients who have tumors exhibiting actionable targets and promoting more informed and accurate treatment decisions [ 81 ]. Mutations in prostate cancer-related genes BRCA1 and BRCA2 render men with mCRPC suitable for treatment with either rucaparib or olaparib, and other prostate cancer genes that have responded well to olaparib treatment, which include ATM , CDK12 , CHECK2 , CHECK1 , PALB2 , PP2R2A, and RAD54L [ 82 ]. The influence of BRCA mutations on therapeutic outcomes in a study of 1302 patients with 67 BRCA mutation carriers was investigated. The results showed that patients who received prostatectomy or radiotherapy developed metastasis and had shorter survival as compared with patients who did not have mutations of the BRCA gene. This study also found that the BRCA1 gene was 12% more common than the BRCA2 gene, which was only 2% common. In a recent study, conducted in 2019, the mutation in the BRCA gene (c.4211C > G) was identified in a Chinese patient treated with radiotherapy and ADT for prostate cancer. The study indicated that prostate cancer patients with this specific mutation were sensitive to ADT as well as radiotherapy, making the treatment more effective [ 83 ]. Mutations that make it difficult to treat or design effective CRPC include the F876L mutation, which changes the binding ligand pocket in the AR. Similarly, the W741L/C mutation stimulates specific AR binding that is able to move AR into its active conformation. Such mutations create obstacles to designing effective treatment for CRPC [ 84 ].

2.5. Treatment and Management of Prostate Cancer

The prognostic factors consisting of initial PSA level, clinical TNM stage, and Gleason’s score have been considered together with other factors such as baseline urinary function, comorbidities, and age as a choice of treatment for prostate cancer [ 85 ]. Advances in prostate cancer diagnosis and treatment have enhanced clinicians’ capacities to classify patients by risk and propose therapy based on cancer prognosis and patient preference [ 86 ]. Surveillance, prostatectomy, and radiotherapy are recognized as the standard treatments for stage I–III prostate cancer patients. Androgen ablation by surgical or pharmacological castration can bring about lasting remission in all stage IV and high-risk stage III patients. In this case, first-generation antiandrogens such as flutamide and bicalutamide can aid. However, in stage IV, castration resistance, which is characterized by genomic mutations in the androgen receptor, invariably occurs, and the prognosis is poor [ 87 ]. Table 4 below summarizes prostate cancer treatment options and their adverse effects.

Common prostate cancer treatment options and potential adverse effects [ 88 ].

2.5.1. Active Surveillance

Active surveillance is a structured program that employs monitoring and expected intervention as the main techniques in the management of prostate cancer [ 89 ]. For patients who have low-risk cancers or those who have a short life expectancy, active surveillance has been recognized as the best option. The criteria for active surveillance have recommendations that are usually based on the following factors: disease characteristics, health conditions, life expectancy, side effects, and patient preference [ 90 ]. The PSA level, clinical progression, or histologic progression are used as prostate cancer trigger points [ 91 ].

The advantages of active surveillance are the preservation of erectile function, decreased costs of treatment, avoidance of needless treatment of inactive cancers, and sustaining life quality and normal activities. Its disadvantages include the likelihood of cancer metastasis before treatment, missed opportunity for a remedy, need for a complex therapy with side effects for larger and aggressive cancers, reduced chances of potency preservation mostly after surgery, chances of increased anxiety by patients, and frequent medical checks [ 92 ].

2.5.2. Radical Prostatectomy

Radical prostatectomy is the procedure of medically removing the prostate gland by open and/or laparoscopic surgery [ 93 ]. The procedure requires making small incisions on the abdomen or via the perineum.

Salvage radical prostatectomy is usually recommended to patients with local recurrence in the absence of metastases after undergoing external beam radiation therapy, brachytherapy, or cryotherapy. This may, however, lead to increased morbidity. Patients younger than age 70 with organ-confined prostate cancer, with a life expectancy higher than 10 years who have little to no comorbidities, are best suited for radical prostatectomy. However, there are a few complications associated with its use. These complications include incontinence and erectile dysfunction arising from surgical damage to the urinary sphincter and erectile nerves [ 94 ].

2.5.3. Cryotherapy

This method involves the use of surgical insertion of cryoprobes into the prostate under ultrasound guidance. It involves freezing of the prostate gland to a temperature from −100 °C to −200 °C for about 10 min. However, there are reports of complications associated with the use of this method, including urinary incontinence and urinary retention, erectile dysfunction, fistula, and rectal pain [ 95 ].

2.5.4. Radiation

Radiation therapy is regarded as one of the most effective therapies that kills prostate cancer cells using high radiations. Radiations are sent to cancerous cells through various techniques such as brachytherapy (the use of seeds placed in the body) and external beam (where the energy is projected through the skin) to the cancerous sites. Radiation therapy aims at specifically transferring high-energy rays or particle doses directly to the prostate without affecting the normal tissues. These doses are based on the level of prostate cancer. This treatment is considered to be an acceptable therapy for patients who are not suited for surgical procedures [ 96 ]. Various techniques of radiation therapy are discussed below.

Brachytherapy

Brachytherapy includes the direct placement of radioactive sources into the prostate gland with the aid of seeds, injections, or wires under the guidance of transrectal ultrasound. This often involves two techniques: low dose and high dose rates. The low dose rate refers to the permanent implantation of seeds in the prostate tissue, which loses radioactivity gradually [ 97 ], and the latter refers to the supply of a dose of radiation to the prostate tissues with significant risk of leakage to other surrounding organs. The advantage associated with brachytherapy is that it can be completed within a day or less. There is a minimal risk of incontinence in patients without a previous transurethral resection of the prostate (TURP). Erectile function is also not affected. Its disadvantages are usually a requirement for general anesthesia, acute urinary retention risks, and persistent irritative voiding symptoms [ 98 ].

External Beam Radiation Therapy

External beam radiation therapy (EBRT) is a commonly used treatment technique that involves emitting strong X-ray beams specifically targeting the prostate tissues. It radiates higher prostate radiation doses, with less emission to the surrounding tissues. Radiation therapy is considered to be an effective intermediate-risk and high-risk prostate cancer treatment when used together with androgen deprivation therapy (ADT) [ 80 ]. It is a suitable therapy for attenuating metastasizing cancer cells. This technique is more advantageous than surgical therapy. It can treat early stages of cancer, and it is associated with fewer risks such as bleeding, myocardial infarction, pulmonary embolus, urinary incontinence, and erectile dysfunction. It can also relieve symptoms such as bone and joint pain [ 93 ]. Side effects of radiation include urinary urgency and frequency, erectile dysfunction, dysuria, diarrhea, and proctitis [ 97 ].

2.5.5. Radium-223 Therapy

The radium-223 dichloride (Xofigo) technique makes use of a substance used for therapy in patients with metastatic prostate cancer that is resistant to hormone therapy. Its ability to mimic calcium makes radium-223 dichloride be selectively absorbed by the cancer cells in bone tissue. This technique has been reported to have a considerable impact on the survival and recovery of metastatic prostate cancer patients, leading to delayed onset of bone fracture and pain [ 85 ].

2.5.6. Hormonal Therapy

Hormonal therapy is also known as androgen deprivation therapy (ADT). This technique is applied in the treatment of advanced and/or metastasized prostate cancer. Its therapeutic mechanism is based on the blockage of testosterone production and other male hormones, preventing them from fueling prostate cancer cells. Therefore, significantly decreased male hormonal levels are responsible for inhibition of the action of androgen on the androgen receptor [ 99 ]. This is often achieved using bilateral orchiectomy or medical castration via administration of luteinizing hormone-releasing hormone (LHRH) analogs or antagonists. LHRH analog primarily elevates the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by stimulating hypophysis receptors, thus, enabling the drug to downregulate the hypophysis receptors with concomitant reduction of LH and FSH levels, leading to suppressed testosterone production. Leuprolide, goserelin, triptorelin, and histrelin are among the common LHRH agonists. The antagonists cause action by blocking the hypophysis receptors, thereby triggering the immediate inhibition of testosterone synthesis [ 100 ]. ADT has, however, been associated with acute and long-term side effects, such as hyperlipidemia, fatigue, hot flashes, flare effect, osteoporosis, insulin resistance, cardiovascular disease, anemia, and sexual dysfunction [ 101 ].

Flutamide is a type of drugnthat is nonsteroidal and pure antiandrogenic lacking hormonal agonist activity. Flutamide is antiandrogen at the androgen-dependent accessory genitals. Its biological activity is based on 2-hydroxyflutamide. Treating prostate cancer with flutamide and an (LHRH) agonist has produced promising results. In vivo studies of flutamide have shown certain antagonist at the ventral prostate and androgen-dependent seminal vesicles [ 102 , 103 ]. Flutamide is known to result in hepatic dysfunction; however, a study on antiandrogen therapy (AAT) in combination with flutamide indicated that flutamide could be successful when performing regular hepatic function testing during treatment periods [ 104 ]. Maximum androgen blockade (MAB) using flutamide as a second-line hormonal therapy can give a prostate-specific antigen response without side effects, making this a possible treatment option for patients with HRPC with no bone metastases or whose cancer has progressed more than a year following first-line therapy [ 105 ].

Chlormadinone acetate (CMA) is an oral steroidal antiandrogen. Chlormadinone has proven to have anticancer activity. Similar to progesterone used in maximum androgen blockade (MAB) therapy as well as monotherapy for prostate cancer in Japan [ 106 ]. To determine the success of the antiandrogen chlormadinone acetate in treating stage A prostate cancer, a study of 111 patients who received chlormadinone acetate was conducted. The progression rates linked to antiandrogen therapy for stage A1 and A2 patients were lesser in non-treatment receiving groups, concluding that antiandrogen treatment with chlormadinone acetate inhibited the progression [ 107 ]. Chlormadinone is also used to treat benign prostatic hyperplasia, it decreases testosterone level, prostate-specific antigen (PSA) level, and prostate volume, in benign prostatic hyperplasia slowing the progression of Prostate cancer [ 108 ].

2.5.7. Abiraterone

Abiraterone is a second-generation therapy targeted at adrenal and tumor androgen production. It is associated with the irreversible inhibition of the hydroxylase and lyase activities of CYP17A, AR pathways, and 3β-hydroxysteroid dehydrogenase activity, and is used to treat prostate cancer that has metastasized to other parts of the body [ 109 ]. Abiraterone has also been proven to be a potent inhibitor of other microsomal drug-metabolizing enzymes, including CYP1A2 and CYP2D6 [ 109 ]. Clinical data of abiraterone have indicated remarkable results, but there are reports of variable responses and concomitant increasing PSA levels. Abiraterone is correlated with high CYP17A upstream mineralocorticoids, with concomitant side effects including edema, hypertension, fatigue, and hypokalemia [ 110 ].

Immunotherapy or biological therapy is based on stimulating or suppressing the immune system. The treatment uses vaccines designed to work with the patient’s immune system to fight cancer cells. Sipuleucel-T (Provenge) is one of such vaccines, designed for advanced and metastatic prostate cancer cells that have developed resistance to hormone therapy. It is developed from the immune cells by collecting the white blood cells and activating them with prostatic acid phosphatase [ 109 ]. This is then associated with a protein that can trigger the immune system before infusing into the blood [ 99 ]. Sipuleucel-T (Provenge, Dendreon) is an autologous dendritic cell-based immunotherapy used in treating asymptomatic patients by assisting a patient’s immune system in fighting back cancer cells. It is intravenously administered in three doses over one month. Its lesser side effects make it more favorable compared to other chemotherapies. Its side effects include fever, nausea, chills, and muscle aches [ 111 ].

2.5.8. Chemotherapy

Chemotherapy uses anticancer drugs to kill or inhibit the growth of cancerous cells. There has been progress in treatment of prostate cancer after decades of learning and understanding genetics, diagnosis, and treatment. The most common chemotherapy drug for prostate cancer is docetaxel (Taxotere) [ 112 ].

Docetaxel is regarded as the first-line standard therapy for prostate cancer cells that are castration-resistant. It is an antimicrotubule agent which attaches to β-tubulin to inhibit microtubule depolymerization, thereby suppressing mitotic cell division and initiating apoptosis [ 113 ]. CYP3A is a major requirement for the activation of Docetaxel. The development of Docetaxel resistance has been associated with relapse. Docetaxel resistance has been attributed to increased upregulation of the multidrug resistance (MDR) 1 gene that encodes P-glycoprotein [ 114 ].

Cabazitaxel

Cabazitaxel is a novel antineoplastic semi-synthetic derived from the needles of various species of yew trees (Taxus). It is usually sold under the name Jevtana. Cabazitaxel is a second-generation therapy aimed at suppressing docetaxel resistance [ 99 ]. It has a low affinity for Pglycoprotein owing to its additional methyl groups. It is metabolized in the hepatic tissues by CYP3A4/5 and CYP2C8 (10–20%). Hypotension, bronchospasm, renal failure, neurotoxicity fatigue, alopecia, and generalized rash/erythema are among the common side effects associated with its use. There have also been reports of diarrheal deaths related to Cabazitaxel therapy resulting in electrolyte imbalances and dehydration [ 114 ].

Enzalutamide

Enzalutamide is a second-generation AR inhibitor that was recognized as one of the chemotherapeutic drugs for prostate cancer in 2012. This drug focuses on the androgen pathway and has functions such as (1) competitively inhibiting the binding of androgen to the androgen receptor, (2) inhibiting nuclear translocation and recruitment of cofactors, and (3) inhibiting the association of the activated androgen receptor. Enzalutamide targets androgens such as testosterone and dihydrotestosterone. Its therapeutic mechanism includes:

• Competitive inhibition of androgen binding to the androgen receptor;
• Inhibition of nuclear translocation and co-factor recruitment;
• Inhibition of the binding of DNA with activated androgen receptor.

The side effects of enzalutamide include fatigue, asthenia, diarrhea, and vomiting [ 115 ].

2.6. Combination Therapy

Combination therapy has been demonstrated as an effective strategy for prostate cancer treatment. Combination therapy is a strategy that was developed to treat castration-resistant prostate cancer and other forms of prostate cancer. There are no drugs to date that treat castration-resistant prostate cancer (CRPC), and currently approved treatment options either used alone or in combination therapy are useful in extending a patient’s lifespan by a few months [ 116 ]. Current treatment options used for the treatment of prostate cancer are not curative, and disease progresses to the castration-resistant phenotype over a period of time. Combination therapy with currently used treatment options for prostate cancer could successfully increase a patient’s lifespan and suppress tumors. Amongst all the available treatment strategies available for metastatic prostate cancer, androgen deprivation therapy (ADT) has more potential combination treatment compared to other therapeutic strategies for prostate cancer, and approved and currently ongoing clinical trials with ADT treatment include ADT with radiation therapy, which often treats high-risk patients to delay or prevent the disease from progressing to CRPC; (ii) ADT and chemotherapy, which in several clinical studies has shown to increase patient survival but results in adverse side effects and sometimes death; and (iii) immunotherapy and ADT, which has been reported to increase patient survival by 8.5 months [ 117 ]. Clinical trials are ongoing to analyze the effects of survival in ADT and the PSA-targeted poxviral vaccine, PROSTVAC-IF; a combination of radiation therapy with immunotherapy under ADT; a combination of chemotherapy with immunotherapy under ADT; and a combination of docetaxel under ADT [ 118 ]. There are a number of completed and ongoing clinical studies/trials for combination therapy of prostate cancer. Some of the clinical trials are listed in Table 5 and Table 6 .

Combination therapies for prostate cancer—completed clinical trials [ 116 ].

Combination therapies for prostate cancer—ongoing clinical trials [ 116 ].

2.7. Drug Repurposing

Drug repurposing, also known as drug repositioning, reprofiling, or retasking, is a way of identifying new uses for approved drugs [ 119 ]. The advantage of drug repurposing over de novo drug development (developing new drugs) is that repurposed drug candidates have undergone extensive research in animal models and clinical trials, testing the safety, optimization, and, in most cases, formulation development of the drug, as well as pharmacokinetic and pharmacodynamic properties. This advantage usually speeds up the research and development for new use of the drug and reduces the failure rate in later efficacy testing clinical trials [ 120 ]. These previously tested drugs can rapidly progress into phase II and phase III human clinical studies, which implies that the associated drug development cost could be drastically deceased. Researchers show great interest in this phenomenon because drug repurposing alleviates the dilemma of some challenges currently faced in clinical research for finding new cancer therapies, such as drug shortage. It can take a period of 10–17 years for a development of a new drug compared to 3–12 years for repurposed drugs. Technology advances play a major role in scanning large databases and detecting key molecular similarities in different diseases to identify drugs that can be repurposed. Androgen deprivation therapy (ADT) is used to treat advanced-stage prostate cancer patients. Metformin is a drug commonly used to treat type II diabetes, repurposed to treat prostate cancer. It can be utilized to sensitize prostate cancer to the currently used standard prostate cancer therapies and improve the efficacy of treatment. It is reported that Metformin is able to increase the effectiveness of ADT for the treatment of prostate cancer [ 121 ]. Here, we discuss three main categories of drug repurposing studies for PCa, classified by different discovery and validation categories, such as the knowledge and ability of the drug to be researched. For example, ormeloxifene, a selective estrogen receptor modulator, is known for its anticancer properties in several cancers such as breast and ovarian cancers, but ormeloxifene is reported to have mediated the inhibition of oncogenic β-catenin signaling and EMT progression in prostate cancer by significantly suppressing β-catenin/TCF-4 transcriptional activity, N-cadherin, MMPs, and triggering pGSK3β expression. The other category is drugs that have been tested in assays and classified in accordance with their activity. For example, Itraconazole, an antifungal drug responsible for preventing angiogenesis and the initiation of the Hedgehog signaling pathway, was experimented in phase II clinical trials and established to be effective in patients with metastatic CRPC [ 122 ]. Table 7 shows different drugs repositioning candidates in prostate cancer clinical trial studies.

Anticancer drug repositioning candidates under clinical investigation for the treatment of prostate cancer [ 32 ].

Other anticancer drugs that are currently being researched in vitro and in vivo for treatment of prostate cancer include naftopidil, an alpha blocker; niclosamide, an anti-helminthic agent; ormeloxifene, an estrogen receptor modulator; nelfinavir, an antiretroviral agent; glipizide, an antidiabetic agent; clofoctol, an antibacterial agent; and triclosan, an antibacterial agent [ 32 ]. Drug repurposing for prostate cancer presents an opportunity to address current treatment challenges. This strategy should be implemented using computational genomic and proteomic tools to assist and guide researchers in their decision making regarding patient treatment [ 122 ].

2.8. Treatment Challenges

Despite the various treatment options, mCRPC remains to be an incurable disease. Over time, the disease continues to develop resistance to different conventional treatment options [ 123 ]. This has led to continuous research on understanding the growth, metastasis, tumorigenesis, tumor microenvironment, and tumor environmental interactions that promote disease progression.

2.8.1. Drug Resistance

Castration resistance has been reported in prostate cancer that has reached advanced stages. Castration resistance allows for androgen signaling via amplification of the androgen receptor’s synthesis of the intra-tumoral hormone, while disrupting the androgen receptor’s coexpressors and coactivators [ 124 ]. Resistance to enzalutamide and abiraterone acetate, as well as gene mutation in metastatic prostate cancer, has been attributed to the overexpression of the active androgen receptor (AR) in patients. Prostate cancer often develops owing to androgens; thus, most treatments are targeted at blocking androgen hormones. This is beneficial to anticancer drug-resistant patients.

Mutations have also been shown to contribute to drug resistance in cancer cells, allowing for bypassing of the targeted pathways. Alterations in intrinsic pathways such as the AR signaling pathways, MAPK/ERK pathway, endothelin A receptor (EAR), and Akt/PI3K pathways as well as exacerbated expression of the androgen receptor have been shown to contribute to ADT resistance [ 46 ].

2.8.2. ABC Transporters

These transporters are expressed in the plasma membrane, where they serve as efflux pumps and are well-known triggers of multidrug resistance. They transport drugs and xenobiotics in and out of the cells [ 125 ]. Multidrug resistance protein (MRP) transporters MRP2, MRP3, MRP4, and MDR-1 protein (P-glycoprotein) have been reported in prostate cancer [ 110 ]. The exacerbated expression of these transporters has been implicated in the increased efflux of drugs, thereby leading to multidrug resistance. Of these transporters, MRP2 has been reported to exhibit the highest potency of resistance to natural product agents, MRP3 exhibits the lowest resistance to etoposide, and MRP4 and MRP5 are responsible for resistance to nucleoside analogs and transport cyclic nucleotides. MRP4 also influences resistance to chemotherapeutic agents such as camptothecins, cyclophosphamide, topotecan, methotrexate, and nucleoside analogs [ 126 ].

2.8.3. Cytochrome P450

Cytochromes P450 are a well-known multigene superfamily of heme-containing monooxygenases that are both constitutive and inducible. They catalyze the metabolism of a variety of xenobiotics and endocrine disruptors [ 127 ]. The family including CYP2C19, CYP4B1, CYP3A5, CYP2D6, CYP1A2, and CYP1B1, has been reported in human prostate cells [ 128 ]. CYP4B1′s main functions are the metabolism and activation of arylamines via N-hydroxylation, an activity that results in bladder tumor [ 129 ]. Exacerbated expression of CYP1B1 has been implicated in the advances of drug resistance in prostate cancers. This is often achieved by 2-hydroxylation of flutamide [ 130 ]. CYP17A speeds up the process of sequential hydroxylase and the lyase steps in the androgen biosynthetic pathway in humans, thus, making it a critical therapeutic marker for prostate cancer treatment [ 131 ].

2.8.4. Mutations in Androgen Receptors

Mutations in androgen receptors occur owing to a disorder in androgen sensitivity. Androgen receptor (AR) signaling plays an important role in the development, activity, and homeostasis of the prostate gland. It regulates the process of gene transcription via attaching to the androgen response elements on specific genes, as well as allowing nuclear translocation of the androgen receptor [ 132 ]. Gene changes in the AR signaling pathway ( Figure 2 ) have been reported in prostate cancers. AR mutations were first reported in an androgen-responsive cell line, LNCap. These mutations have been implicated in the development of AR resistance arising from AR-targeted therapy [ 133 ]. This has led to the use of androgen deprivation therapy (ADT) and antihormone therapy in the treatment of advanced prostate cancer. The majority of AR mutations result in single amino acid substitutions, which are mostly found in the AR androgen-binding domain. The mutation T877A, which has been found in roughly 30% of metastatic CRPC patients, is the most common [ 134 ]. Other mutations have resulted in enhanced AR binding to coregulators, resulting in higher AR transcriptional activity vis-à-vis H874Y and W435L mutations. These mutations have been implicated in the development of AR resistance arising from AR-targeted therapy [ 124 ]. Figure 3 illustrates the transcription activity of the androgen receptor gene [ 135 ].

The function of AR signaling in prostate cancer and development: ( A ) Prostate homeostasis is maintained in a healthy prostate via reciprocal signaling between the stromal and epithelial layers; ( B ) normal prostate cells are converted into cancer initiating cells by unknown mechanisms, histological evidence of prostatic intraepithelial neoplasia and early cancer lesions appears, cells at the basal layer express higher levels of AR in response to this event; ( C ) cellular and molecular alterations occur in prostate adenocarcinoma, resulting in luminal cells with the AR transcriptional pathway; ( D ) Prostate cancer cells in CRPC maintain AR activity through other mechanisms (including upregulation of AR and its splice variants, intra-tumoral androgen synthesis, cross communicate with other signal pathways, and increased/altered expression of AR cofactors) as the availability of androgen from the blood steam becomes limited [ 134 ].

The androgen receptor gene encodes a 110 kD protein composed of 919 amino acids that are classified by an androgen-binding domain (ABD), a conserved DNA-binding domain (DBD), and an N-terminal transactivation domain, which has two polymorphic trinucleotide repeat segments. These repeated segments, consisting of variable numbers of polyglycine repeats and polyglutamine, highly influence the androgen receptor transcription activity. The gene transcript consists of eight exons in total: exon 1 codes for the N-terminal domain, exons 2–3 code for the DBD, and exons 4–8 code for the ABD [ 135 ].

2.8.5. Tumor Microenvironment

The tumor microenvironment has a crucial role in the development and progression of prostate cancer to the advanced stage, as per recent studies. According to experimental research, the milieu and malignant tumor cells have a mutually reinforcing relationship in which early changes in the microenvironment of normal tissue can foster carcinogenesis and tumor cells can foster more protumor modifications in the microenvironment [ 136 ]. A tumor microenvironment comprises a wide interlinked niche encompassing the extracellular matrix and specialized cells such as neural cells, blood vessels, immune cells, and mesenchymal/stromal stem cells, all of which secrete factors such as chemokines, cytokines, and matrix-degrading enzymes. They interact with cancer cells through paracrine and autocrine mechanisms [ 137 , 138 ].

According to a tumor stage-specific histological investigation, high-grade PC is linked to enhanced stromal immune cell infiltrates with a variety of cellular types [ 139 ]. Chronic stresses such as direct infection, urine reflux, a high-fat diet, and estrogens affect the prostate’s ability to become inflamed on a long-term basis [ 140 ]. The stromal compartment experiences an inflow of several immune cells, including CD3+ T-cells, macrophages, and mast cells, amid ongoing inflammation [ 141 ]. High levels of cytokines and chemokines, primary tumor necrosis factor, nuclear factor kappa B, to mention a few, are produced by inflammatory cells. The regulation of angiogenesis, cellular proliferation, and inflammation involves these proteins among others. They control the PC’s shift to the malignant phenotype [ 136 ].

The surrounding stromal agents go through complex modifications as a result of the interaction between prostatic epithelial cells and the tumor microenvironment, and these changes control the severity of the disease, its capacity to spread, and its susceptibility to traditional treatments [ 142 , 143 ].

2.9. Role of Estrogen Receptors (ERs) in Prostate Cancer Etiology and Progression

Prostate cancer is often regarded as hormone dependent, since steroid hormones direct its initiation and progression. Earlier reports have emphasized the significance of steroid levels in the etiology of PCa [ 144 , 145 ]. Estrogen plays an indispensable role in the secretion of male sex hormones, and it also plays cardinal roles in the growth, differentiation, and homeostasis of prostate tissues. Estrogens also contribute to the development of prostate cancer [ 146 ]. In a report from Ellem and Risbridger using aromatase knockout (KO) mice, the knockout mice could not metabolize androgens to estrogens, and it was observed that high levels of testosterone led to the development of prostate gland enlargement (prostatic hyperplasia). Meanwhile, increased estrogen and decreased testosterone levels gave rise to inflammatory events and lesions [ 147 ]. Epidemiological studies have also proposed that the serum level of estradiol and the serum estradiol/testosterone (E/T) ratio influence the initiation of PC and its progression [ 148 ]. Estrogen activities are carried out by two receptors, which are estrogen receptor α (ERα) or β (ERβ); ERα and Erβ are expressed in prostate tissue [ 125 ]. ERα is confined to the prostatic stroma, and has an indirect effect on the epithelial cells, while ERβ is found to be expressed within the epithelial domain and regulates epithelial proliferation and differentiation [ 149 ]. No less than five ERβ homologues (ERβ1, -2, -3, -4, and -5) exist in humans [ 145 ]. ERβ1 plays a functional role, while the other isoforms control its activity. The role of ERβ may consequently depend on the ratio of expression of ERβ1 and ERβ isoforms. It is known that ERα brings about the adverse effects induced by estrogens, while ERβ directs the protective and anti-apoptotic effects of estrogen in PCa [ 149 ]. On the one hand, the expression of estradiol receptor α has been found to be remarkably linked with a high Gleason’s score and poor survival rate in patients with PCa [ 150 ]; on the other hand, ERβ expression was found to be decreased or lost in the examined PCa samples [ 151 ]. Furthermore, the expression of ERβ2 and ERβ5 together has been shown to constitute a marker for biochemical relapse, post-surgery spread/metastasis, and the period to spread after radical prostatectomy in PCa patients. Based on the aforementioned, the expression of ERβ1 decreased, and that of ERβ2 and ERβ5 increased with the progression of PCa. This expression pattern corresponded with the spreading and metastasis of PCa [ 152 ]. In PCa, on the one hand, ERα has an oncogenic role and directs the deleterious effects of estrogen, which include proliferation, inflammation, and prostate carcinogenesis. Erβ, on the other hand, may elicit antitumor activity (oncosuppressor) in PCa manipulation of ERβ by ligands. Novel drug candidates might be useful in the therapeutic strategies towards PCa, specifically during the earlier stages of the disease [ 145 ].

2.10. Experimental Work Exploring Alternative Treatments

Traditional medicine in prostate cancer medicine in prostate cancer treatment.

Traditional medicine plays a significant role in healthcare in developing countries, and such countries also have a long history of treating different diseases and ailments. The use of medicinal plants in cancer has gained substantial attention, and recently, research is ongoing, with the National Cancer Institute (NCI) playing a pivotal role in the research of traditional medicine to treat cancer [ 153 ]. Traditional medicine is used significantly by patients with cancer to minimize side effects or used entirely as a single treatment rather than conventional therapy. This is because plants are easily accessible, effective, and affordable. Plant-derived compounds and plant extracts have been widely used due to their anti-inflammatory, antioxidant, and antimicrobial properties [ 154 ]. Various anticancer agents used in therapy today are derived from plants, for example, paclitaxel and taxol are derived from Taxus brevifolia , docetaxel (Taxotere) from Taxus baccata , and vincristine and vinblastine from Catharanthus roseus [ 155 ].

There is considerable proof supporting the utilization of a plant-based diet for the prohibition of acute disorders. Consumption of plant-based food provides necessary nutritional supplements and phytochemicals that aid in growth and shield against the occurrence of various acute illnesses [ 156 ]. They also offer protection against oxidative stress related to chronic disorders such as cancer. Phenolic compounds serve protective roles including antibacterial, anti-inflammatory, and anticancer roles [ 157 ]. Plants containing organosulfur compounds have chemoprotective activity. Carotenoids and polyphenols have anti-inflammatory and antioxidant activity [ 158 ]. Consequently, medicinal plants are commonly used for the treatment of cancers [ 159 ]. Several flavonoids have shown anticancer activity in the treatment of prostate cancer. Flavonoids are polyphenolic compounds characterized by a benzene ring condensed with a six-member phenyl ring attached to the carbon 2 and carbon 3 (C2 and C3) carbon positions. Among flavonoids, flavonols which can be identified by a distinctive hydroxyl group at the carbon 3 carbon position, have been reported in a number of studies, both preclinical and clinical, for their anticancer activity in prostate cancer cell lines. Flavonols, myricetin, fisetin, and kaempferol are commonly found in several fruits and vegetables and display anti-inflammatory, antiviral, antineoplastic, antibacterial, and antioxidant activity, among many others, in different cells [ 160 ].

Several specific plants have been analyzed for their activity as anticancer agents for cancer treatment. Plant anticancer activity is linked to phytochemical constituents present in extracts. Table 8 summarizes various medicinal plants used in cancer treatment [ 161 ].

Summary of various medicinal plants used against different types of cancers [ 161 ].

2.11. Gene Therapy

The developments achieved in genetics, biotechnology, tumor biology, and immunology have facilitated new advancements in gene therapy. Gene therapy is a therapy that includes inserting or deleting a DNA sequence or base pair to rectify a genetic defect in a specific protein or to target a certain molecular pathway. A few gene editing technologies are currently being developed for gene therapy. Gene therapies usually involve the encapsulation of DNA nucleotides into viral and non-viral vectors that deliver the gene to a specific site, then, inserting the gene into the human genome to edit the DNA sequence and regulate cellular processes [ 162 ]. The main idea of gene therapy is to deliver exogenous nucleotides to specific DNA parts in the cells of various tissues. Viruses are well known for being efficient in transferring their genome into a host to infect it. The viral vector can be administered intravenously by injecting it directly into the targeted tissue. Non-viral vectors such as nanoparticles and polymers have also been studied for their use in gene therapy for the treatment of prostate cancer. These non-viral vectors usually condense DNA through electrostatic interactions, which also protects the genetic material from degrading. Gene therapies also explore the use of apoptosis. Failure of cells to undergo apoptosis can lead to uncontrolled cell division, which then leads to the development of cancer [ 163 ]. The suppression of apoptosis usually occurs as a result of the genetic mutations in cancerous cells. Gene therapy for prostate cancer targets apoptosis cellular pathways by introducing a gene that encodes a mediator or inducer of apoptosis in defective cells encoding an inducer, mediator, or executioner of apoptosis. Apoptosis-inducing genes, such as caspases, induce cell death in cancer cells [ 164 ]. Numerous challenges such as enhancing DNA transfer efficiency to cells, as well as immune responses that interfere with gene expression lie ahead for gene therapy. However, irrespective of the difficulties, it is definite that gene therapy will be the next up-and-coming medical technique used against prostate cancer in the future. Some clinical trial studies investigating prostate cancer therapy using gene therapy include various transgenes such as p53 and herpes simplex tk [ 165 ]. Recently used prostate cancer gene therapy procedures involve rectifying abnormal gene expression, utilizing programmed cell death mechanisms and biological pathways, specifically targeting important cell functions, initiating mutant or cell lytic suicide genes, strengthening the immune system anticancer response, and connecting treatment with radiation therapy or chemotherapy [ 166 ]. Animal studies in prostate cancer gene therapy have made use of intraprostatic administration of gene therapy delivery systems. This route of administration has been found to be more effective, as most of the dose was delivered directly to the prostate. This targeted delivery allowed the administered dose to reach prostate cancer metastasis. Lactoferrin and transferrin are multifunctional proteins that can bind to iron-binding proteins that are usually overexpressed on prostate cancer cells [ 167 ]. The proteins are responsible for regulating free iron levels. High iron levels have negative side effects such as increasing the risk of bacterial infections, as well generating free radicals and promoting the conversion of oxidation states ferrous ion (Fe2+) to ferric ion (Fe3+). Various studies in animals have used transferrin and lactoferrin for active targeting of prostate cancer cells. Prostate stem cell antigen (PSCA) is a cell surface antigen that is expressed in androgen-dependent and androgen-independent prostate cancer cells; therefore, it can be used as a marker for prostate cancer. Human epidermal growth factor receptor 2 (HER2) is another ligand that can be used as a marker for targeted treatment of prostate cancer due to mutations causing overexpression of tumor cells [ 168 ]. A study conducted on prostate cancer-induced xenograft mice models indicated that the inhibition of HER2 and epidermal growth factor receptor (EGFR) by specifically targeting tumor-initiating cells could highly improve the efficacy of the chemotherapy treatment for castration-resistant prostate cancer with activated STAT3, and could prevent metastasis EGF-induced STAT3 phosphorylation, which is responsible for enabling prostate cancer metastasis [ 169 , 170 ]. Various gene targeting systems have experimented on immune response treatment with a DAB-Lf dendriplex encoding IL12, which has demonstrated drastic tumor reduction in the PC3 and DU145 prostate tumors. MiRNA (miR)-205, miR-455-3p, miR-23b, miR-221, miR-222, miR-30c, miR-224, and miR-505 are downregulated in patients with prostate cancer and are known to be associated with tumor suppressors in prostate cancer cells, affecting proliferation, invasion, and aerobic glycolysis. MiR-663a and miR-1225-5p are linked to the development of prostate cancer, showing potential to be used as candidate markers. The specific functions of miR-663a and miR-1225-5p in stimulating prostate cancer growth and tumor progression are unclear [ 171 , 172 , 173 ].

2.12. CRISPR Cas9

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is a natural defense mechanism found in archaea and bacteria. This system is currently being extensively researched because of its simplicity and effectiveness [ 145 ]. The ability to target intraprostatic inoculation of specific gene therapy vectors is an advantage of immunotherapy-based and cytotoxic gene therapy approaches. Because changes in DNA sequences result in mutations that cause cancer, scientists have been interested in new approaches to correct such changes by manipulating DNA [ 174 ]. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system uses single-guide RNA (sgRNA) to identify and bind to certain DNA sequences through Watson–Crick base pairing [ 175 ]. CRISPR and the CRISPR–Cas9 (CRISPR-associated 9) system have been extensively studied and have changed the study of biological systems. CRISPR allows the precise altering, inserting, or deleting of DNA nucleotides in the target DNA sequence by initiating double-strand breaks. A guide RNA binds to Cas9, leading it to a complementary DNA target sequence, where a double-strand break is inserted to repair or edit DNA nucleotides. CRISPR can also be used for detecting DNA from RNA from cancerous cells and cancer-causing viruses. CRISPR/Cas9 delivery in nanoparticle lipid-based vectors is safer to use and effective [ 176 ]. Liposomal vectors offer a wide range of advantages and modifications, giving direct control over the physico-chemical properties of the liposomal surface, and can accommodate the conjugation of targeting ligands. An antibody-targeted delivery system of lipid nanoparticles (LNPs) was initially developed and standardized for the targeted treatment with small interfering RNA (siRNA). Recently, LNPs were used in a proof-of-concept study to target disseminated ovarian cancer in mice with CRISPR/Cas9 [ 177 ]. A study by Ye et al., 2017, analyzed the function of GPRC6A in the progression of prostate cancer progression in vitro and in animal studies. The study indicated that GPRG6A was expressed in human prostate cancer cell lines, and also showed polymorphism that improved mTOR signaling. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 nuclease (Cas9) (CRISPR/Cas9) were used to interrupt the GPRC6A gene in the PC-3 cell line. The results indicated that editing the GPRC6A gene using CRISPR/Cas9 stopped cell proliferation and migration in vitro, and also that osteocalcin activated the ERK, AKT, and mTOR signaling pathways. It was found that the GPRC6A gene mediated the progression of prostate cancer in animal studies mainly through assessing the response to osteocalcin in human prostate cancer xenograft models with cells expressing GPRC6A gene or the CRISPR/Cas9-mediated deletion of the gene. The findings of the study supported the use of CRISPR as a potential therapeutic target [ 178 ]. The first genome-scale CRISPRi screen in metastatic PCa models indicated that kinesin family member 4A (KIF4A) and WD repeat domain 62 (WDR62) initiate aggressive PCa. Novel targets for prostate cancer are also provided by CRISPR screen in prostate-specific cell lines, also suggesting the importance of assessing the results in other cancer cells, which may lead to the discovery of biomarkers for prostate cancer therapy [ 179 ].

2.13. Nanotechnology

Nanotechnology is an integrative field that combines pharmacology, biomedical science, and nanotechnology. Nanoparticles have characteristics that allow drug efficacy, can easily penetrate tumors, prevent drug degradation, and can be modified to target specific tissues [ 170 ]. Nanoparticles such as liposomes, polymers, metal nanomaterials, and porous silicon nanoparticles have been highly researched for application in prostate cancer treatment and prognosis. Active targeting nanoparticles have modified surfaces with attached antibodies, affibodies, peptides, or oligosaccharides. These targeting ligands target receptor cells on cancerous cells, such as the prostate-specific membrane antigen (PSMA) receptors on prostate cancer cells [ 180 ]. There is interest in developing nanoparticles for prostate cancer therapy due to challenges faced by currently used treatments. A study conducted at Mount Sinai New York on 16 patients used gold silica nanoparticles for localized prostate cancer. The gold silica nanoparticles absorbed infrared light at a wavelength that could penetrate biological tissues. The gold nanoparticles possessed plasmon resonance that could drastically decrease side effects related to the therapy. Patients were injected intravenously with gold nanoparticles with laser ablation. The growth of the tumor was analyzed using magnetic resonance imaging after 48 and 72 h of therapy. The results showed a decrease in tumor size with no side effects. While only a few studies have progressed to clinical trials, a study on targeted and controlled release for prostate cancer therapy has recently started clinical trials, which has led to the development of the BIND-014 docetaxel encapsulated nanoprototype [ 155 ]. The results of preclinical and clinical improvements linked to liposomal drug delivery in cancer treatment suggest that liposomal encapsulation signals a positive future for the treatment of prostate cancer. Nanocarriers have been demonstrated as useful in combination therapy, as they are able to overcome differences in pharmacokinetics in chemotherapeutic agents [ 173 ]. Combining nanotechnology and other therapeutic strategies can effectively enhance and improve the effectiveness of drugs. In prostate cancer, nanotechnology is used in diagnostics and therapeutic treatment. Not only are nanoparticles effective delivery systems, but they also improve the solubility of poorly soluble drugs, and multifunctional nanoparticles display adequate specificity toward urological cancers, bladder, renal, and prostate cancer. In a study conducted by Zhang et al., the encapsulation of docetaxel and doxorubicin in nanoparticles increased the observed cytotoxicity in prostate cancer cells [ 180 ]. Another study, conducted to assess the codelivery of doxorubicin (DOX) and docetaxel (DOC) by nanocarriers for synergistic activity, suggested that both anticancer agents DOX and DOC in the nanoparticles acted synergistically and promoted the curative effect of Dox and Doc in a xenograft mouse model, which acted on androgen-dependent and androgen-independent prostate cancer cell lines [ 181 ]. A multicenter phase II open-label clinical trial consisting of 42 patients with progressing mCRPC who received abiraterone acetate and/or enzalutamide treatment studied the safety and efficacy of a docetaxel-containing nanoparticle (BIND-014) targeting prostate-specific membrane antigen (PSMA) in metastatic castration-resistant prostate cancer. Targeted delivery of docetaxel by prostate-specific membrane antigen (PSMA)-conjugated nanoparticles was found to be clinically effective, drastically reducing circulating tumor cells [ 182 ]. A modern method of heating tumors after inoculation of magnetic nanoparticles has been extensively researched in prostate cancer clinical trials. The feasibility and tolerability were evaluated with the first prototype of an alternating magnetic field applicator in a study experimenting with magnetic nanoparticle thermotherapy alone or in combination with permanent seed brachytherapy. The results reported that magnetic nanoparticle thermotherapy had been shown to be hyperthermic and effective to thermoablative temperatures and could be achieved in the prostate at low magnetic field strengths of 4–5 kA/m [ 183 , 184 ].

2.14. Next-Generation Sequencing

Recently, the development of next-generation sequencing (NGS) technologies has proven to be a substantial advancement in the documentation of unique genetic alterations that have improved our understanding of cancer cell biology [ 185 ]. Precision medicine, also known as personalized medicine, strives to produce individualized treatment plans and do away with “one-size-fits-all” approaches to therapy [ 186 ]. The development of personalized treatment was supported by NGS, which not only increased our understanding of cancer but also gave oncologists a strong tool for understanding each patient’s disease and its distinct genetic characteristics and whole-genome mutational status [ 187 , 188 ]. NGS can identify tumor-specific alterations with single-nucleotide resolution [ 189 ]. The NGS technologies are whole-genome, whole-exome, RNA, reduced representation bisulfite, and chromatin immunoprecipitation sequencing. The three crucial phases in NGS are library preparation and amplification, sequencing, and data analysis [ 190 ]. Even though the Sanger sequencing and PCR methods have long been used to examine tumor biomarkers, the development of NGS has made it possible to screen more genes in a single test. Predictive biomarkers have subsequently been developed to assist in selecting the right patient populations for clinical investigations. Additionally, NGS enables researchers to identify the most prevalent known variants as well as the long tail of uncommon mutations that occur in less than 1% of patients and can offer helpful data on treatment sensitivity [ 187 ].

The application of NGS in PC genomics has significantly advanced the systematic cataloging of all DNA alterations occurring in cancer [ 188 ]. The identification and production of novel long non-coding RNAs and novel gene fusions in PC have been greatly aided by the use of RNA sequencing. This has resulted in the discovery of new recurrent alterations that have been identified, which are TMPRSS2-ERG translocation, SPOP and CHD1 mutations, and chromoplexy, and also the pathways that have been previously well-established have been validated (e.g., androgen receptor overexpression and mutations; PTEN, RB1, and TP53 loss/mutations) [ 189 , 190 ]. DNA sequencing is now far more sensitive and scaleable due to NGS [ 191 ]. PC continues to present a significant challenge in terms of diagnosis and prognosis due to its highly diverse nature [ 192 ]. To more accurately determine the cancer’s aggressiveness, clinicopathological and radiological data should be combined with the knowledge gathered from NGS investigations [ 193 , 194 ]. Despite having great hopes for NGS benefits, there are a number of limitations to the method that should be taken into consideration [ 194 ]. Firstly, there are valid arguments against NGS replacing established and thoroughly supported histopathological diagnoses. Although NGS can often be utilized to identify and subtype various cancer entities, an accurate pathological examination should always come first [ 195 ]. Second, NGS from tumor biopsies only provides limited temporal and geographical resolution of the entire tumor since it can only evaluate DNA and RNA changes in a small group of tumor cells at a particular timepoint [ 196 ]. This issue can be approached from a variety of angles, including improving spatial resolution through novel techniques, single-cell sequencing, serial analysis of circulating cell-free nucleic acids or tumor cells, or pragmatically focusing on the actionability of specific targets via functional studies [ 197 ]. Third, the creation of the software tools required for the analysis and clinical interpretation of the “big data” produced by NGS to support clinical decision making is still lagging behind the hardware infrastructure that is currently in place for its calculation, management, and storage [ 198 ]. Additionally, significant bioinformatical work is required to directly compare data obtained on various NGS platforms and evaluated by various bioinformatic pipelines and algorithms. Therefore, the success of NGS and precision oncology depends greatly on efficient communication and constructive teamwork among all parties [ 199 ].

3. Conclusions

Prostate cancer is one of the leading causes of death in men globally, after lung disease. Commonly mutated genes, proteins, and pathways associated with an increased risk of prostate cancer development can be used as biomarkers for the disease, which provide information on the stage and cause of cancer. Biomarkers can also give specifications on the type of treatment required for cancer. There is an urgent need for effective and targeted specific treatment for prostate cancer. The current treatments available for prostate cancer are beneficial to only a few patients, and present numerous side effects that eventually affect the quality of life of most patients. Chemotherapy, radiotherapy, and hormonal treatment have adverse side effects, including drug resistance, which remains a setback to anticancer treatment. Many medicinal plants, gene therapy, and the application of nanotechnology currently in research have proven to reduce side effects as well as restore chemosensitivity in resistant tumor cells. Medicinal plant fractions and compounds, genetic material encapsulated in target-specific nanocarriers with controlled release, and targeted therapies based on cellular pathways appear to be promising alternatives for prostate cancer treatment.

Funding Statement

Reference: TTK200415513610, NRF grant no 129891.

Author Contributions

M.S., supervision—oversight and leadership of the research, planning and execution, critical review and editing of the manuscript, funding acquisition; K.R., summary, introduction, abstract, genetics, diagnosis, treatment options, alternative approaches, conclusion and referencing, review and editing, project administration; P.M., summary, introduction, abstract, genetics, diagnosis, treatment options, alternative approaches, conclusion and referencing; L.G., summary, introduction, abstract, diagnosis, treatment options, alternative approaches, conclusion referencing; A.A., genetics, treatment options, critical review and editing of the manuscript; S.M., review and editing of the manuscript. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Data availability statement, conflicts of interest.

The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of this review.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Elacestrant in ER + , HER2 − Metastatic Breast Cancer with ESR1 -Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy plus CDK4/6 Inhibitor and in Clinical Subgroups

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Bardia A, Bidard FC, Neven P, et al. EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+/HER2− metastatic breast cancer: updated results by duration of prior CDK4/6 inhibitors in metastatic setting. Presented at: San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS3-01.

Bardia A, O’Shaughnessy J, Bidard FC, et al. Elacestrant versus standard-of-care in ER+/HER2− advanced or metastatic breast cancer (mBC) with ESR1 mutation: key biomarkers and clinical subgroup analyses from the phase 3 EMERALD trial. Presented at: San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. PS17-02.

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Aditya Bardia , Javier Cortés , François-Clément Bidard , Patrick Neven , José Garcia-Sáenz , Phillipe Aftimos , Joyce O’Shaughnessy , Janice Lu , Giulia Tonini , Simona Scartoni , Alessandro Paoli , Monica Binaschi , Tomer Wasserman , Virginia Kaklamani; Elacestrant in ER + , HER2 − Metastatic Breast Cancer with ESR1 -Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy plus CDK4/6 Inhibitor and in Clinical Subgroups. Clin Cancer Res 2024; https://doi.org/10.1158/1078-0432.CCR-24-1073

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Elacestrant significantly prolonged progression-free survival (PFS) with manageable safety versus standard-of-care (SOC) endocrine therapy (ET) in patients with estrogen receptor–positive (ER + ), HER2 − metastatic breast cancer and tumors harboring estrogen receptor 1 ( ESR1 ) mutation following ET plus a cyclin-dependent kinase 4/6 inhibitor (ET+CDK4/6i). In patients with ESR1 -mutated tumors, we evaluated the efficacy and safety of elacestrant versus SOC based on prior ET+CDK4/6i duration and in clinical subgroups with prior ET+CDK4/6i ≥12 months.

EMERALD, an open-label phase III trial, randomly assigned patients with ER + , HER2 − metastatic breast cancer who had received 1–2 prior lines of ET, mandatory CDK4/6i, and ≤1 chemotherapy to elacestrant (345 mg daily) or SOC (aromatase inhibitor or fulvestrant). PFS was assessed across subgroups in post hoc exploratory analyses without adjustment for multiple testing.

In patients with ESR1 -mutated tumors and prior ET+CDK4/6i ≥12 months, the median PFS for elacestrant versus SOC was 8.6 versus 1.9 months (HR, 0.41; 95% confidence interval, 0.26–0.63). In this population, the median PFS (in months) for elacestrant versus SOC was 9.1 versus 1.9 (bone metastases), 7.3 versus 1.9 (liver and/or lung metastases), 9.0 versus 1.9 (<3 metastatic sites), 10.8 versus 1.8 (≥3 metastatic sites), 5.5 versus 1.9 ( PIK3 catalytic subunit α mutation), 8.6 versus 1.9 (tumor protein p53 gene mutation), 9.0 versus 1.9 (HER2-low), 9.0 versus 1.9 ( ESR1 D538G -mutated tumors), and 9.0 versus 1.9 ( ESR1 Y537S/N -mutated tumors). Subgroup safety was consistent with the overall population.

The duration of prior ET+CDK4/6i ≥12 months in metastatic breast cancer was associated with a clinically meaningful improvement in PFS for elacestrant compared with SOC and was consistent across all subgroups evaluated in patients with ER + , HER2 − , ESR1 -mutated tumors.

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• Introduction
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This study examined ovarian cancers in individuals who underwent opportunistic salpingectomy (OS) compared with a control group who underwent hysterectomy alone and tubal ligation.

Error bars denote 95% CIs.

a Denotes a cell size of less than or equal to 5, not an exact number.

eTable. Additional Details From Registry Sources

eReferences

• Salpingectomy in Ovarian Cancer Prevention JAMA Viewpoint June 20, 2023 This Viewpoint explains the use of opportunistic salpingectomy, removal of the fallopian tubes for the primary prevention of ovarian cancer in a woman already undergoing pelvic surgery for another indication. Rebecca Stone, MD, MS; Joseph V. Sakran, MD, MPH, MPA; Kara Long Roche, MD, MSc

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Hanley GE , Pearce CL , Talhouk A, et al. Outcomes From Opportunistic Salpingectomy for Ovarian Cancer Prevention. JAMA Netw Open. 2022;5(2):e2147343. doi:10.1001/jamanetworkopen.2021.47343

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Outcomes From Opportunistic Salpingectomy for Ovarian Cancer Prevention

• 1 Division of Gynaecologic Oncology, Department of Gynaecology and Obstetrics, The University of British Columbia, Vancouver, British Columbia, Canada
• 2 Vancouver General Hospital Research Pavilion, Vancouver, British Columbia, Canada
• 3 Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor
• 4 Pathology & Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
• Viewpoint Salpingectomy in Ovarian Cancer Prevention Rebecca Stone, MD, MS; Joseph V. Sakran, MD, MPH, MPA; Kara Long Roche, MD, MSc JAMA

Question   Is opportunistic salpingectomy associated with fewer than expected ovarian cancers?

Findings   This population-based cohort study included 25 889 individuals who underwent opportunistic salpingectomy and 32 080 individuals who underwent hysterectomy alone or tubal ligation. There were no serous ovarian cancers among individuals in the opportunistic salpingectomy group, which was significantly lower than the age-adjusted expected rate of 5.27 serous cancers.

Meaning   The opportunistic salpingectomy group had significantly fewer serous ovarian cancers than expected, suggesting that opportunistic salpingectomy is associated with reduced ovarian cancer risk.

Importance   Opportunistic salpingectomy (OS), which is the removal of fallopian tubes during hysterectomy or instead of tubal ligation without removal of ovaries, is recommended to prevent ovarian cancer, particularly serous ovarian cancer. However, the effectiveness of OS is still undetermined.

Objective   To examine observed vs expected rates of ovarian cancer among individuals who have undergone OS.

Design, Setting, and Participants   This is a population-based, retrospective cohort study of all individuals in British Columbia, Canada, who underwent OS or a control surgery (hysterectomy alone or tubal ligation) between 2008 and 2017, with follow-up until December 31, 2017. Those with any gynecological cancer diagnosed before or within 6 months of their procedure were excluded. Data analysis was performed from April to August 2021.

Exposures   Removal of both fallopian tubes at the time of hysterectomy or instead of tubal ligation while leaving ovaries intact.

Main Outcomes and Measures   An ovarian cancer diagnosis listed in the British Columbia Cancer Registry. Age-specific rates of epithelial and serous ovarian cancer in the control group were combined with the specific follow-up time in the OS group to calculate expected numbers (and 95% CIs) of ovarian cancers in the OS group. These were compared with observed numbers. Age-adjusted expected and observed numbers of breast and colorectal cancers were also examined in the OS group.

Results   There were 25 889 individuals who underwent OS (mean [SD] age, 40.2 [7.1] years; median [IQR] follow-up, 3.2 [1.6-5.1] years) and 32 080 who underwent hysterectomy alone or tubal ligation (mean [SD] age, 38.2 [7.9] years; median [IQR] follow-up, 7.3 [4.6-8.7] years). There were no serous ovarian cancers in the OS group and 5 or fewer epithelial ovarian cancers. The age-adjusted expected number was 5.27 (95% CI, 1.78-19.29) serous cancers and 8.68 (95% CI, 3.36-26.58) epithelial ovarian cancers. Age-adjusted expected vs observed numbers of breast cancers (22.1 expected vs 23 observed) and colorectal cancers (9.35 expected vs 8 observed) were not significantly different.

Conclusions and Relevance   In this cohort study, the OS group had significantly fewer serous and epithelial ovarian cancers than were expected according to the rate at which they arose in the control group. These findings suggest that OS is associated with reduced ovarian cancer risk.

Approximately 70% of sporadic and nearly all ovarian cancers in BRCA variant carriers are high-grade serous carcinomas (HGSCs), 1 which is the most lethal of the 5 main histotypes and has a 5-year survival rate less than 50%. 2 Although the general population lifetime risk of ovarian cancer is 1.4%, 3 individuals with an inherited germline BRCA1 or BRCA2 variant have average cumulative risks of 40% to 75% and 8% to 34%, respectively. 4 In BRCA 1/2 variant carriers, bilateral salpingo-oophorectomy is recommended, which reduces the risk of ovarian or fallopian tube cancers by 80%. 5 Removal of the ovaries is not recommended for the general population because it is associated with increased total mortality, coronary heart disease, and osteoporosis. 6 Thus, a different preventive strategy is needed for individuals at average risk, who account for 80% of cases of HGSCs.

The recent understanding that HGSC often originates in the fallopian tube 7 , 8 has led to a primary prevention opportunity for the general population—namely, opportunistic salpingectomy (OS). OS collectively refers to the removal of the fallopian tubes at the time of hysterectomy or instead of tubal ligation, while leaving the ovaries intact. In 2010, the British Columbia (BC) ovarian cancer research team launched a province-wide strategy asking gynecologists to discuss OS with their patients as an ovarian cancer prevention strategy. The same recommendation has since been made in many countries, including Canada, the US, and the UK for individuals without identified genetic factors associated with increased risk of ovarian cancer. 9 - 12 Research has shown that OS is safe, both in terms of perioperative adverse events 13 and minor complications, 14 there are no indications of an earlier age of onset of menopause following OS, 15 and it is cost-effective. 16

Some retrospective data from individuals who underwent bilateral salpingectomy for conditions such as hydrosalpinx and pelvic inflammatory disease have suggested decreased risk of ovarian cancer among individuals without fallopian tubes. 17 - 19 However, we hypothesize that OS is associated with more protection than salpingectomies done for diseases that directly affect and distort the fallopian tube, because the intent of OS is complete removal of the fimbriated end of the fallopian tube, which may not occur when salpingectomy is done for other indications. Finally, these historical studies did not use the appropriate control groups, as OS is recommended only for individuals already undergoing gynecological surgery, and both hysterectomy and tubal ligation are associated with protection against ovarian cancer. 20 Here, we examine observed rates of ovarian cancer and compare these with expected rates (based on age-adjusted rates of ovarian cancer in the control group of individuals who underwent hysterectomy alone or tubal ligation).

This population-based, retrospective, cohort study examined data on all residents of the Canadian province of BC (population, 5 million). All individuals who underwent a hysterectomy or tubal sterilization in BC between 2008 and 2017 were included. Approvals were obtained from all relevant data stewards, and access to the Consolidation file, the BC Cancer Registry, the Discharge Abstract Database, and the BC Cancer Agency Screening Program was facilitated through Population Data BC. More details, including citations to data sources, are presented in the eTable in the Supplement . Ethics approval was obtained from the University of British Columbia’s Behavioral Research Ethics Board. Approval by the ethics board and the BC data stewards for use of deidentified administrative data files includes a waiver of informed consent from participants. This study follows the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline. 21

Individuals who underwent any of the relevant surgical procedures were identified using the Canadian Classification of Health Intervention codes. This system separately identifies each procedure performed during the same surgery, and a person undergoing a hysterectomy with bilateral salpingectomy has both a code indicating the removal of the uterus and one indicating the removal of the fallopian tubes. Individuals with a diagnosis of any gynecological cancer before or within 6 months of their surgery were excluded, as this cancer was likely present at the time of surgery. Individuals were stratified into 2 groups according to their procedures: (1) those who underwent OS, meaning they had a hysterectomy with a salpingectomy but no oophorectomy, or they had a bilateral salpingectomy alone with a diagnosis code indicating the procedure was for sterilization ( International Statistical Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code Z.30.2), and (2) those who underwent control surgical procedures, which included those who had undergone a hysterectomy with no concomitant oophorectomy or salpingectomy and anyone who underwent a tubal ligation.

In BC, cancer is a reportable disease, and all cases are entered into the provincial cancer registry. The registry sources include hematology and pathology reports, death certificates, hospital reports, and cancer treatments (see the eTable in the Supplement for more details). All ovarian cancers were identified using the International Classification of Diseases for Oncology (ICD-O) codes for ovarian cancer ( ICD-O code C56.X), fallopian tube cancer ( ICD-O code C57.0), or peritoneal cancer, not otherwise specified ( ICD-O code C48.2). All epithelial ovarian cancers diagnosed after a surgery of interest were included, and borderline tumors were excluded. ICD-O morphology codes were used to identify the histotype of the ovarian cancers according to the algorithm published by Peres et al. 22 The grade data were incomplete, and all serous cancers were presented together rather than as low grade and high grade; however, 95% of serous cancers are HGSCs. To examine whether differences in the observed and expected ovarian cancers in the OS group might be explained by underlying differences in the likelihood of getting cancer associated with health status, lifestyle, genetics, and so forth, differences in observed and age-adjusted expected numbers of breast cancer ( ICD-O code C50) and colorectal cancer ( ICD-O code C18.X) but excluding cancer of the appendix ( ICD-O code C18.1) were also examined.

We examined how the groups differed with respect to potentially important confounders, including age at the time of surgery, income quintiles, parity, gravidity, history of oral contraceptive pill use and total mean days of oral contraceptive use, presence of a known BRCA variant, and the presence of benign gynecological conditions at the time of surgery, including endometriosis ( ICD-10-CM code N80.X), leiomyoma ( ICD-10-CM code D25.X), benign ovarian or uterine neoplasm ( ICD-10-CM codes D26.X, D27.X, and D28.7), abnormal bleeding ( ICD-10-CM codes N92.X and N93.X), pelvic organ prolapse ( ICD-10-CM code N81.X), pelvic inflammatory disease ( ICD-10-CM codes N73.X and N74.X), and hydrosalpinx ( ICD-10-CM code N70.X).

For privacy reasons, data steward agreements require that we not publish cell sizes between 1 and 5. The number of observed epithelial and serous ovarian cancers in the OS group are presented according to privacy requirements. We also present the number of observed breast and colorectal cancers. These observed numbers were then compared with the number expected on the basis of age-adjusted (in 5-year age groups) rates in the control group multiplied by the person-time contribution in the OS group. Given the low number of ovarian cancers in both groups, statistical models were not run. Instead the distribution of the potential confounders across the OS and control groups and their standardized differences were presented. A difference between covariates was considered meaningful if the standardized difference was greater than 0.1. 23

The age-adjusted rates of serous ovarian cancers were also used to project the number of expected serous ovarian cancers in the OS group 5 and 10 years beyond our study period if serous ovarian cancers were to occur at the same rate as in the control group. To project, we used data from the cohort included in our control group and adjusted the person-time contribution in each age group as individuals in the cohort age. Data were analyzed using Stata statistical software version 16 (StataCorp). Data analysis was performed from April to August 2021.

Before exclusions, there were 60 153 individuals who underwent any of the surgical procedures of interest. After exclusion of 74 individuals who were younger than age 15 years at the time of surgery and 2110 individuals with cancers that were diagnosed before or within 6 months of surgery, there were 25 889 individuals (mean [SD] age, 40.2 [7.1] years) in the OS group, including 14 066 who underwent hysterectomy with OS and 11 823 who underwent OS for sterilization. There were 32 080 individuals (mean [SD] age, 38.2 [7.9] years) in the control group, including 10 446 individuals who underwent hysterectomy alone and 21 634 who underwent tubal ligation ( Figure 1 ). The Table compares the characteristics of the OS groups (hysterectomy with OS and OS for sterilization) with the control groups (hysterectomy alone and tubal ligation). There were no meaningful differences in any oral contraceptive pill use (18 098 individuals [69.9%] in the OS group vs 21 414 individuals [66.8%] in the control group), duration of oral contraceptive pill use (OS group, mean [SD], 757 [1091] days and median [IQR], 265 [0-1080] days; control group, mean [SD], 662 [965] days and median [IQR], 218 [0-960] days), and BRCA variant rates between the groups (27 individuals [0.10%] in the OS group vs 34 individuals [0.11%] in the control group). Individuals who underwent OS were older at the time of surgery (mean [SD], 40.2 [7.1] vs 38.2 [7.9] years), had fewer live births (mean [SD], 1.74 [1.29] vs 2.03 [1.33] live births) and fewer pregnancies (mean [SD], 2.26 [1.87] vs 2.63 [1.93] pregnancies), and were more likely to have endometriosis (3301 individuals [12.8%] vs 2279 individuals [7.1%]) than those in the control group. There was longer follow-up in the control group vs the OS group (median [IQR], 7.3 [4.6-8.7] vs 3.2 [1.6-5.1] years).

Figure 2 A illustrates that there were no serous cancers in the OS group by the end of follow-up. Given the age-adjusted rate at which serous ovarian cancers occurred in the control group and the follow-up time in the OS group, 5.27 (95% CI, 1.78-19.29) serous cancers were expected. The same is true for all epithelial ovarian cancers. The expected number of epithelial ovarian cancers in the OS group was 8.68 (95% CI, 3.36-26.58) cancers, and the actual number was less than or equal to 5 (exact number not presented to protect patient privacy) ( Figure 2 B). In contrast, there were 15 serous cancers in the control group, and 21 epithelial ovarian cancers (including 6 nonserous cancers). Figures 2 C and 2 D show no significant differences between expected and observed numbers of breast or colorectal cancers in the OS group. The age-adjusted expected number of breast cancers in the OS group was 22.1 (95% CI, 11.62-49.37) cancers, and 23 breast cancers were observed in this group. The age-adjusted expected number of colorectal cancers in the OS group was 9.35 (95% CI, 3.13-30.11) cancers, and 8 cancers were observed.

Figure 3 shows projections of serous cancers in the OS group if they arise at the same rate as those in the control group. Because there were no serous cancers in the OS group, we cannot estimate exactly how many of these serous cancers will be prevented. If OS were not performed, we would expect an estimated 36.9 (95% CI, 12.2-127.7) serous cancers by 2022 and 45.1 (95% CI, 14.7-157.5) cancers by 2027. These numbers do not account for additional individuals being added to the OS group.

The realization that the fallopian tube fimbriae is the tissue of origin for most HGSCs opened the door for OS as a primary ovarian cancer prevention strategy. 8 Prevention of ovarian cancer seems more critical today than ever as the largest screening trial found that although a stage shift was achieved, there was no mortality benefit. 24 In BC in 2010, a population-wide primary prevention campaign was initiated to remove the fallopian tubes of individuals at general population risk for ovarian cancer when they were undergoing hysterectomy for benign indications or seeking tubal ligation. The acceptability, safety, and cost-effectiveness of this OS campaign has already been established. 13 - 16 In this cohort study, we now present data strongly suggesting that OS is effective as an ovarian cancer primary prevention strategy at the population level. There was not a single serous ovarian cancer in the OS group, which was significantly fewer than the slightly more than 5 that were expected. We have further shown that the OS group had the same risk of breast and colorectal cancers compared with the control group, indicating that the lack of ovarian cancers in the OS groups is unlikely to be associated with selection bias. The rates of common risk and protective factors for the OS group place them at slightly higher risk of ovarian cancer (eg, lower parity, lower gravidity, and higher age), indicating that our results are unlikely to be explained by confounding.

There were 15 serous cancers observed in the control group, and our calculations show that as we continue follow-up, there will be 45.1 serous ovarian cancers in this group by 2027. It is difficult to determine the preventable fraction given that we did not observe any serous cancers in our OS group. The least conservative interpretation would be that OS prevents all serous cancers, but more realistically it is probably more in line with the prevention achieved by risk-reducing salpingo-oophorectomy in patients with a BRCA variant, which is on the order of 80%. 5 For example, if an estimated 200 000 individuals underwent hysterectomy without salpingectomy and a tubal ligation (instead of an OS) in Canada between 2011 and 2016, then on the basis of a 1% lifetime risk of HGSC and an assumed 80% effectiveness of OS, 1600 future cases of HGSC could theoretically have been prevented. Thus, although the numbers presented here are small, uptake of OS on a larger scale could be associated with the incidence of HGSCs nationally and internationally.

These findings may also further our understanding of the origin for HGSCs. Twenty years ago in a provocative editorial, 25 it was suggested that the ovarian surface epithelium may not be the tissue of origin for ovarian carcinomas. Shortly afterward, detailed analysis of fallopian tubes and ovaries from BRCA variant carriers found tubal dysplastic lesions, now called serous tubal intraepithelial carcinomas, but no ovarian pathology. 26 Systematic analysis of fallopian tubes and ovaries in many studies has since shown that serous tubal intraepithelial carcinomas are found in individuals with BRCA variants, also alongside sporadic and incidental HGSCs but not in the general population. 7 , 27 - 30 Genomic studies have confirmed the clonal association between serous tubal intraepithelial carcinomas and HGSC, and transgenic mice with mutated fallopian tube cells produce histologically perfect HGSCs. 31 , 32 However, there are data supporting potential primary ovarian origins of some HGSCs, including mouse models and expression data; thus, it is possible that some HGSCs arise from ovarian surface epithelium or endosalpingiosis. 33 , 34 However, despite detailed analysis in many studies, credible ovarian HGSC precursors have not been described. Ultimately, expansion of the data presented here will determine the relative portion of HGSCs that originate in the fallopian tube vs the ovary.

Our findings are consistent with previous epidemiological research from the US, Denmark, and Sweden, 17 - 19 which studied the association between excisional tubal surgery or salpingectomy and the risk of ovarian cancer among individuals with a medical indication for these procedures. The observed relative risks showed a 42% to 65% reduction in risk of ovarian cancer for individuals who underwent a major surgical procedure involving the fallopian tube. 17 - 19 Furthermore, tubal ligation has long been recognized as being inversely associated with ovarian cancer risk, although the magnitude of the association is lower than those for the more extensive fallopian tube procedures mentioned already. 35

Our work has some important limitations, including that these are observational data and not derived from a randomized clinical trial; thus, selection factors could introduce bias. However, the Table illustrates that there are few differences between the OS group and control group with respect to the most well-known risk and protective factors for ovarian cancer (eg, parity, oral contraceptive pill use, BRCA variant status, and endometriosis), and the differences that do exist would bias toward increased risk for ovarian cancer in the OS group. Although it remains possible that there are important unmeasured differences between the groups, such as lifestyle factors that are associated with cancer, the findings of no difference between the observed and expected numbers of breast and colorectal cancers in the OS group suggest that selection bias is unlikely to explain these results. The study was limited by the small number of cancers and relatively short follow-up time in our groups. Although uptake of OS has been substantial in BC, the province has a relatively small population (approximately 5 million), and the surgical procedures at which OS is performed occur at young mean ages. Thus, our numbers of ovarian cancers were small, making it impossible to run Cox proportional hazards models controlling for potential confounders. In addition, although the preliminary data suggest that there are no indicators of an earlier age of onset of menopause, it is time to conduct a long-term follow-up study on the age of onset of menopause as self-reported by those who undergo OS or a control surgery. Given the reduction in observed ovarian cancer compared with expected, which strongly supports reduced risk of ovarian cancer following OS, it is important to ensure OS does not alter the age of onset of menopause.

This study found significantly smaller numbers of observed ovarian cancers compared with expected numbers for patients who underwent prophylactic OS at the time of hysterectomy or instead of tubal ligation. Most professional gynecological societies around the world have recommended consideration of OS. Our findings strengthen the evidence for presenting this option to patients at average risk of ovarian cancer. These data may also aid in patient decision-making around contraception options following childbearing.

Accepted for Publication: December 15, 2021.

Published: February 9, 2022. doi:10.1001/jamanetworkopen.2021.47343

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2022 Hanley GE et al. JAMA Network Open .

Corresponding Author: Gillian E. Hanley, PhD, Vancouver General Hospital Research Pavilion, 590-828 W 10th Ave, Vancouver, BC V5Z 1M9, Canada ( [email protected] ).

Author Contributions: Dr Hanley had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Huntsman and Miller are co–final authors and contributed equally to this work.

Concept and design: Hanley, Talhouk, Finlayson, McAlpine, Huntsman, Miller.

Acquisition, analysis, or interpretation of data: Hanley, Pearce, Kwon, McAlpine, Huntsman.

Drafting of the manuscript: Hanley, Kwon.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Hanley, Pearce, Talhouk, Kwon.

Obtained funding: Hanley, Talhouk, Finlayson.

Administrative, technical, or material support: Hanley, Finlayson, Miller.

Supervision: Kwon, McAlpine.

Conflict of Interest Disclosures: Dr Kwon reported receiving grants from Astra Zeneca outside the submitted work. No other disclosures were reported.

Funding/Support: This research was supported by funding from the Canadian Institutes of Health Research, the Janet D. Cottrelle foundation, and the Vancouver General Hospital and University of British Columbia Hospital Foundation. Dr Hanley is supported by a Canadian Institutes of Health Research New Investigator Award, a Michael Smith Foundation for Health Research Scholar award, the Canadian Cancer Society Research Institute, and is a Janet D. Cottrelle Foundation scholar.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: All inferences, opinions, and conclusions are those of the authors and do not reflect the opinions or policies of the Data Stewards.

Additional Contributions: We thank the general gynecologists in British Columbia, Canada, for enthusiastically following the 2010 recommendation for opportunistic salpingectomy. Without their support, this research would not have been possible.

Additional Information: Researchers can apply to access these data, available to any interested researchers through Population Data BC ( http://www.popdata.bc.ca ) following ethics approval, completion of a data access request, and approval of that data access request by all relevant data stewards.

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Biden Awards $150 Million in Research Grants as Part of Cancer ‘Moonshot’

President Biden has had a deep personal interest in cancer research since his son Beau died of an aggressive brain cancer in 2015.

President Biden Announces $150 Million in Cancer Research Grants

President biden said eight research centers would receive research awards aimed at pioneering new methods of precision cancer surgery as part of his administration’s cancer “moonshoot” initiative..

As all of you know, cancer surgery is an incredibly challenging procedure. It takes the best surgeons in the world, and it takes its toll on families. As Jill and I — as Jill says, it steals time. It steals away hope. Our family knows the feeling, as many here do. Today, we’re announcing $150 million ARPA-H funding for some of the nation’s cutting-edge cancer research institutions. That includes, right here, Tulane University. [cheers] And we’re moving quickly because we know all families touched by cancers are in a race against time. It’s all part of our goal, of our cancer “moonshot,” to end cancer as we know it. Even cure some cancers. We’re mobilizing the whole of country effort to cut American cancer deaths in half by — within 25 years, and boost support for patients and their families. I’m confident in our capacity to do that.

By Zach Montague

Reporting from New Orleans

Freed from the campaign trail and the grinding pursuit of another term, President Biden traveled to New Orleans on Tuesday to focus on a project close to his heart: the “moonshot” effort to sharply cut cancer deaths in the United States that he carried over from his time as vice president and has become a hallmark of his presidency.

Speaking at Tulane University, Mr. Biden and the first lady, Jill Biden, announced eight research centers, including one at Tulane, that will collectively receive $150 million in research awards aimed at pioneering new methods of precision cancer surgery.

Before addressing a crowd on campus, the president and the first lady met with a team of researchers who demonstrated the technology under development at Tulane. It uses imaging of cells on tumor sites to verify for surgeons that cancer cells have been fully removed and to reduce the need for follow-up surgeries.

Standing in front of a sign reading “curing cancer faster,” Mr. Biden described touring cancer centers in Australia and Ireland, and being frustrated by a lack of international collaboration.

“We don’t want to keep information — we want to share it,” he said.

The awards announced on Tuesday are to be made through the Advanced Research Projects Agency for Health , or ARPA-H, which was founded in 2022 and is aimed at driving biomedical innovation.

The other award recipients were Dartmouth College; Johns Hopkins University; Rice University; the University of California, San Francisco; the University of Illinois Urbana-Champaign; the University of Washington; and Cision Vision in Mountain View, Calif.

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Watch CBS News

Cancer deaths among men predicted to increase 93% by 2050, study finds

By Sara Moniuszko

Edited By Allison Elyse Gualtieri

Updated on: August 12, 2024 / 7:41 PM EDT / CBS News

Cancer cases and deaths among men are expected to surge globally by 2050, according to a new study.

In the study , published Monday in Cancer, a peer-reviewed journal of the American Cancer Society, researchers projected an 84% increase in cancer cases and a 93% increase in cancer deaths among men worldwide between between 2022 and 2050.

The increases were greater among men 65 and older and in countries and territories with a low or medium human development index. The index measures each country's development in health, knowledge and standard of living, according to the study. 

Using data from the Global Cancer Observatory, the study analyzed more than 30 different types of cancers across 185 countries and territories worldwide to make demographic projections.

"We know from previous research in 2020 that cancer death rates around the world are about 43% higher in men than in women," said CBS News chief medical correspondent Dr. Jon LaPook. "So this study today looked at, OK, what do we expect over the next 25 years? And it turns out that it translates to about 5 million more deaths per year in men in 2050, compared to today."

This isn't the first study to paint a less-than-optimistic outlook at the future of cancer case numbers.

Earlier this year, the World Health Organization predicted we will see more than 35 million new cancer cases by 2050, a 77% increase from the estimated 20 million cases in 2022. The survey looked at both men and women in 115 countries.

The organization pointed to several factors behind the projected global cancer increase, including:

• Population aging and growth
• Changes to people's exposure to risk factors, with air pollution a key driver of environmental risk factors
• Tobacco and alcohol use 

In the latest study, authors also pointed to smoking and alcohol consumption as modifiable risk factors prevalent among men.

"By far, not smoking is the single most important thing" people can do do reduce their risk, LaPook said. 

Other factors that may help explain why men face higher rates of cancer compared to women include lower participation in cancer prevention activities and underuse of screening and treatment options, the study authors said. 

Improving access to cancer prevention, screening, diagnosis and treatment options, especially for older men, could help improve cancer outcomes, lead author Habtamu Mellie Bizuayehu said in  a news release .

Sara Moniuszko is a health and lifestyle reporter at CBSNews.com. Previously, she wrote for USA Today, where she was selected to help launch the newspaper's wellness vertical. She now covers breaking and trending news for CBS News' HealthWatch.

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Collection  10 March 2022

Top 100 in Cancer

This collection highlights our most downloaded* cancer papers published in 2021. Featuring authors from aroud the world, these papers showcase valuable research from an international community.

*Data obtained from SN Insights which is based on Digital Science's Dimensions.

Radiotherapy for brain metastasis and long-term survival

• Kawngwoo Park
• Gi Hwan Bae
• Jaehun Jung

The Angelina Jolie effect: Contralateral risk-reducing mastectomy trends in patients at increased risk of breast cancer

• Narendra Nath Basu
• James Hodson
• D. Gareth Evans

Deep learning classification of lung cancer histology using CT images

• Tafadzwa L. Chaunzwa
• Ahmed Hosny
• Hugo J. W. L. Aerts

Pancancer survival analysis of cancer hallmark genes

• Gyöngyi Munkácsy
• Balázs Győrffy

Anti-estrogenic and anti-aromatase activities of citrus peels major compounds in breast cancer

• Dina M. El-Kersh
• Shahira M. Ezzat
• Mohey M. Elmazar

Arsenic exposure in Indo Gangetic plains of Bihar causing increased cancer risk

• Mohammad Ali
• Ashok Kumar Ghosh

CIBERSORT analysis of TCGA and METABRIC identifies subgroups with better outcomes in triple negative breast cancer

• Kelly E. Craven
• Yesim Gökmen-Polar
• Sunil S. Badve

The incidence and clinical analysis of non-melanoma skin cancer

• Magdalena Ciążyńska
• Grażyna Kamińska-Winciorek
• Aleksandra Lesiak

Real-world outcomes versus clinical trial results of immunotherapy in stage IV non-small cell lung cancer (NSCLC) in the Netherlands

• Christine M. Cramer-van der Welle
• Marjon V. Verschueren
• The Santeon NSCLC Study Group

Anti-tumour activity of deer growing antlers and its potential applications in the treatment of malignant gliomas

• Louis Chonco
• Tomás Landete-Castillejos
• Tomás Segura

Risk of cancer development in patients with keloids

• Hung-Pin Tu
• Chih-Hung Lee

Neutrophil to lymphocyte ratio influences impact of steroids on efficacy of immune checkpoint inhibitors in lung cancer brain metastases

• Bicky Thapa
• Manmeet S. Ahluwalia

Prediction of survival in patients with advanced, refractory colorectal cancer in treatment with trifluridine/tipiracil: real-world vs clinical trial data

• Ana Fernández Montes
• Alberto Carmona-Bayonas
• Teresa Garcia García

Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

• Shao-Yuan Chen
• Koichi Tsuneyama
• Shih-Ming Huang

Histopathological analysis of mucinous breast cancer subtypes and comparison with invasive carcinoma of no special type

• Michał Piotr Budzik
• Marta Magdalena Fudalej
• Anna Maria Badowska-Kozakiewicz

Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT

• Guiyang Hao
• Tara Mastren
• Xiankai Sun

Associations between the gut microbiome and fatigue in cancer patients

• Joud Hajjar
• Tito Mendoza

cGAS–STING cytosolic DNA sensing pathway is suppressed by JAK2-STAT3 in tumor cells

• Manuel Adrian Suter
• Nikki Y. Tan
• Y. L. Zhang

Iodine containing porous organosilica nanoparticles trigger tumor spheroids destruction upon monochromatic X-ray irradiation: DNA breaks and K-edge energy X-ray

• Yuya Higashi
• Kotaro Matsumoto
• Fuyuhiko Tamanoi

COVID-19 engages clinical markers for the management of cancer and cancer-relevant regulators of cell proliferation, death, migration, and immune response

• Serhiy Souchelnytskyi
• Andriy Nera
• Nazariy Souchelnytskyi

High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials

• Haowen Xiao

Sensitivity, specificity, and accuracy of a liquid biopsy approach utilizing molecular amplification pools

• Jessica Garcia
• Nick Kamps-Hughes
• Cristian Ionescu-Zanetti

A survival analysis of surgically treated incidental low-grade glioma patients

• Lingcheng Zeng

Integrated multi-omics analysis of ovarian cancer using variational autoencoders

• Muta Tah Hira
• M. A. Razzaque
• Mosharraf Sarker

Cell-free DNA concentration and fragment size as a biomarker for prostate cancer

• Emmalyn Chen
• Clinton L. Cario
• John S. Witte

Real-world outcomes of first-line pembrolizumab plus pemetrexed-carboplatin for metastatic nonsquamous NSCLC at US oncology practices

• Vamsidhar Velcheti
• Thomas Burke

Graphene oxide loaded with tumor-targeted peptide and anti-cancer drugs for cancer target therapy

Comprehensive analysis of metastatic gastric cancer tumour cells using single-cell RNA-seq

• Yingyi Zhang
• Xianbao Zhan

Ex vivo culture of intact human patient derived pancreatic tumour tissue

• John Kokkinos
• George Sharbeen
• Phoebe A. Phillips

A phase 2a clinical study on the safety and efficacy of individualized dosed mebendazole in patients with advanced gastrointestinal cancer

• S. Mansoori

Palliative radiation therapy for symptomatic advance breast cancer

• Galia Jacobson
• Orit Kaidar-Person
• Merav Akiva Ben-David

Deep learning identifies morphological features in breast cancer predictive of cancer ERBB2 status and trastuzumab treatment efficacy

• Dmitrii Bychkov
• Nina Linder
• Johan Lundin

A prostate-specific membrane antigen (PSMA)-targeted prodrug with a favorable in vivo toxicity profile

• Srikanth Boinapally
• Hye-Hyun Ahn
• Martin G. Pomper

Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer

• Franceska Dedeurwaerdere
• Kathleen BM Claes
• Geert Martens

Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications

• Fengqin Shi

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20 + B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis

• Chengxin Luo

Morphofunctional analysis of human pancreatic cancer cell lines in 2- and 3-dimensional cultures

• Fuuka Minami
• Norihiko Sasaki
• Toshiyuki Ishiwata

Potentiality of multiple modalities for single-cell analyses to evaluate the tumor microenvironment in clinical specimens

• Yukie Kashima
• Yosuke Togashi
• Toshihiko Doi

Polysaccharide hydrogel based 3D printed tumor models for chemotherapeutic drug screening

• Aragaw Gebeyehu
• Sunil Kumar Surapaneni
• Mandip Singh

PTEN loss promotes oncogenic function of STMN1 via PI3K/AKT pathway in lung cancer

• Guangsu Xun

Co-culture model of B-cell acute lymphoblastic leukemia recapitulates a transcription signature of chemotherapy-refractory minimal residual disease

• Stephanie L. Rellick
• Gangqing Hu
• Laura F. Gibson

Effect of SSRI exposure on the proliferation rate and glucose uptake in breast and ovary cancer cell lines

• Britta Stapel
• Catharina Melzer

Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

• Erik Brodin
• Paul Macklin

Pembrolizumab in vaginal and vulvar squamous cell carcinoma: a case series from a phase II basket trial

• Jeffrey A. How
• Amir A. Jazaeri

Relationship of breast volume, obesity and central obesity with different prognostic factors of breast cancer

• Daniel María Lubián López
• Carmen Aisha Butrón Hinojo
• Ernesto González Mesa

Meta-analysis of host transcriptional responses to SARS-CoV-2 infection reveals their manifestation in human tumors

• Fengju Chen
• Yiqun Zhang
• Chad J. Creighton

Selection and characterisation of Affimers specific for CEA recognition

• Shazana Hilda Shamsuddin
• David G. Jayne
• Paul A. Millner

Epidemiology and prognosis in young lung cancer patients aged under 45 years old in northern China

Real-world data of fulvestrant as first-line treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer

• M. Ruiz-Borrego

Classification of paediatric brain tumours by diffusion weighted imaging and machine learning

• Niloufar Zarinabad
• Andrew Peet

Metagenomic analysis of formalin-fixed paraffin-embedded tumor and normal mucosa reveals differences in the microbiome of colorectal cancer patients

• Gabriela Debesa-Tur
• Vicente Pérez-Brocal
• Andrés Moya

A novel proteomics approach to epigenetic profiling of circulating nucleosomes

• Priscilla Van den Ackerveken
• Alison Lobbens
• Marielle Herzog

A review and comparison of breast tumor cell nuclei segmentation performances using deep convolutional neural networks

• Andrew Lagree
• Majidreza Mohebpour
• William T. Tran

Comparative analysis of machine learning approaches to classify tumor mutation burden in lung adenocarcinoma using histopathology images

• Apaar Sadhwani
• Huang-Wei Chang
• Peter Cimermancic

Alteration of DNA mismatch repair capacity underlying the co-occurrence of non-small-cell lung cancer and nonmedullary thyroid cancer

• Shiro Fujita
• Katsuhiro Masago

Anticancer potential of rhizome extract and a labdane diterpenoid from Curcuma mutabilis plant endemic to Western Ghats of India

• T. Lakshmipriya
• P. R. Manish Kumar

Serum-derived exosomal PD-L1 expression to predict anti-PD-1 response and in patients with non-small cell lung cancer

• Yoshihisa Shimada
• Jun Matsubayashi
• Norihiko Ikeda

Transcript levels of keratin 1/5/6/14/15/16/17 as potential prognostic indicators in melanoma patients

• Guo-Liang Shen

Enhancing the landscape of colorectal cancer using targeted deep sequencing

• Chul Seung Lee
• In Hye Song
• Sung Hak Lee

PGMD/curcumin nanoparticles for the treatment of breast cancer

• Mankamna Kumari
• Nikita Sharma
• Surendra Nimesh

GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients

• Fahimeh Afzaljavan
• Ayeh Sadat Sadr
• Alireza Pasdar

Explainable drug sensitivity prediction through cancer pathway enrichment

• Yi-Ching Tang
• Assaf Gottlieb

A novel biosensor for the ultrasensitive detection of the lncRNA biomarker MALAT1 in non-small cell lung cancer

• Dongming Wu

Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression

• Siyuan Cheng

New combination chemotherapy of cisplatin with an electron-donating compound for treatment of multiple cancers

• Qinrong Zhang
• Qing-Bin Lu

Lung adenocarcinoma and lung squamous cell carcinoma cancer classification, biomarker identification, and gene expression analysis using overlapping feature selection methods

• Joe W. Chen
• Joseph Dhahbi

Similarities between pandemics and cancer in growth and risk models

• Lode K. J. Vandamme
• Ignace H. J. T. de Hingh
• Paulo R. F. Rocha

Flavonoids increase melanin production and reduce proliferation, migration and invasion of melanoma cells by blocking endolysosomal/melanosomal TPC2

• Ponsawan Netcharoensirisuk
• Carla Abrahamian
• Christian Grimm

Convolutional autoencoder based model HistoCAE for segmentation of viable tumor regions in liver whole-slide images

• Mousumi Roy
• Vandana Mukherjee

Low temperature plasma irradiation products of sodium lactate solution that induce cell death on U251SP glioblastoma cells were identified

• Hiromasa Tanaka
• Masaru Hori

CAD systems for colorectal cancer from WSI are still not ready for clinical acceptance

• Sara P. Oliveira
• Pedro C. Neto
• Jaime S. Cardoso

Applicability of pan-TRK immunohistochemistry for identification of NTRK fusions in lung carcinoma

• Simon Strohmeier

Sulforaphane induces S-phase arrest and apoptosis via p53-dependent manner in gastric cancer cells

• Huazhang Wu

Repositioning metformin and propranolol for colorectal and triple negative breast cancers treatment

• L. E. Anselmino
• M. V. Baglioni
• M. Menacho Márquez

Evaluation of wavelength ranges and tissue depth probed by diffuse reflectance spectroscopy for colorectal cancer detection

• Marcelo Saito Nogueira
• Siddra Maryam
• Stefan Andersson-Engels

C. elegans -based chemosensation strategy for the early detection of cancer metabolites in urine samples

• Enrico Lanza
• Martina Di Rocco
• Viola Folli

Detection of colorectal cancer in urine using DNA methylation analysis

• R. D. M. Steenbergen

Learning deep features for dead and living breast cancer cell classification without staining

• Gisela Pattarone
• Laura Acion
• Emmanuel Iarussi

Epidemiological overview of multidimensional chromosomal and genome toxicity of cannabis exposure in congenital anomalies and cancer development

• Albert Stuart Reece
• Gary Kenneth Hulse

Adipose-derived mesenchymal stem cells differentiate into heterogeneous cancer-associated fibroblasts in a stroma-rich xenograft model

• Yoshihiro Miyazaki
• Tatsuya Oda
• Yasuyuki S. Kida

Loss of Parkinson’s susceptibility gene LRRK2 promotes carcinogen-induced lung tumorigenesis

• Chandra Lebovitz
• Nicole Wretham
• Sharon M. Gorski

Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer

• Tadanobu Shimura
• Priyanka Sharma

Differential expression of PD-L1 between primary and metastatic epithelial ovarian cancer and its clinico-pathological correlation

• Sandeep Kumar Parvathareddy
• Abdul K. Siraj
• Khawla S. Al-Kuraya

Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer

• Ryoichi Katsube
• Kazuhiro Noma
• Toshiyoshi Fujiwara

Prognostic gene expression signatures of breast cancer are lacking a sensible biological meaning

• Kalifa Manjang
• Shailesh Tripathi
• Frank Emmert-Streib

Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts

• Miguel Martin
• Rocio Ramos-Medina
• Sara Lopez-Tarruella

Evidence for improved prognosis of colorectal cancer diagnosed following the detection of iron deficiency anaemia

• Orouba Almilaji
• Sally D. Parry
• Jonathon Snook

CDC2-like (CLK) protein kinase inhibition as a novel targeted therapeutic strategy in prostate cancer

• Sean R. Porazinski
• Michael R. Ladomery

Prognostic value of prostate volume in non-muscle invasive bladder cancer

• Won Sik Ham
• Jee Soo Park
• Jongchan Kim

Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells

• Nobuki Matsumoto
• Miku Ebihara
• Toru Imamura

A prognostic model for colorectal cancer based on CEA and a 48-multiplex serum biomarker panel

• Kajsa Björkman
• Sirpa Jalkanen
• Caj Haglund

Breath biopsy of breast cancer using sensor array signals and machine learning analysis

• Hsiao-Yu Yang
• Yi-Chia Wang
• Chi-Hsiang Huang

Targeting the DNA replication stress phenotype of KRAS mutant cancer cells

• Tara Al Zubaidi
• O. H. Fiete Gehrisch
• Henning Willers

CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

• Nataliia Petruk
• Sanni Tuominen
• Katri S. Selander

Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies

• Marina Stasenko
• David R. Spriggs

The clinical significance of microvascular invasion in the surgical planning and postoperative sequential treatment in hepatocellular carcinoma

• Wentao Wang

Elevated levels of mitochondrial CoQ 10 induce ROS-mediated apoptosis in pancreatic cancer

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• Anne R. Diers
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Evaluation of dose-volume histogram prediction for organ-at risk and planning target volume based on machine learning

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Parvimonas micra , Peptostreptococcus stomatis, Fusobacterium nucleatum and Akkermansia muciniphila as a four-bacteria biomarker panel of colorectal cancer

• Muhammad Afiq Osman
• Hui-min Neoh
• Rahman Jamal

Abiraterone acetate versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer

• Takashi Ueda
• Takumi Shiraishi
• Osamu Ukimura

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Page 1 of 7

High-frequency ultrasound-assisted drug delivery of chia, cress, and flax conjugated hematite iron oxide nanoparticle for sono-photodynamic lung cancer treatment in vitro and in vivo

Sono-photodynamic therapy (SPDT), which combines photodynamic (PDT) and sonodynamic (SDT) therapies with sensitizers, offers new avenues for cancer treatment. Even though new sensitizers for SPDT have been syn...

• View Full Text

Maximizing oxaliplatin's impact on EGFR + colorectal cancer through targeted extracellular vesicles

To investigate the ability of extracellular vesicles (EVs) to deliver oxaliplatin to epidermal growth factor receptor (EGFR + ) colorectal cancer cells and increase oxaliplatin’s cytotoxicity.

Towards using fluorescent nanodiamonds for studying cell migration

Since wound healing requires cells to repopulate a damaged area, cell migration is essential. In addition, migration plays a crucial role in cancer metastasis. Whether tumour cells can invade tissue and metast...

Biosynthesized silver nanoparticles of Cissus woodrowii inhibit proliferation of cancer cells through induction of apoptosis pathway

The purpose of this study was biogenic synthesis of silver nanoparticles using aqueous leaf extract of Cissus woodrowii (CW-AgNPs) and exploration of their role in inhibition cell proliferation of breast cancer c...

Acoustic waves and smart biomimetic nanoparticles: combination treatment from 2D to 3D colorectal cancer models

Colorectal Cancer (CRC) is the second leading cause of death among tumors worldwide. Conventional treatments are often accompanied by emerging immunotherapies, trying to reduce the burden of advanced and metas...

Correction: Targeting and internalizing PEGylated nanodrugs to enhance the therapeutic efficacy of hematologic malignancies by anti-PEG bispecific antibody (mPEG × CD20)

The original article was published in Cancer Nanotechnology 2023 14 :78

Retraction Note: Green synthesis of oncolytic Newcastle disease virus-loaded thiolated chitosan nanoformulation for CD44 targeted delivery and sustained release of virus in cervical cancer xenografts

Retraction note: evaluation of the anticancer potential of cd44 targeted vincristine nanoformulation in prostate cancer xenograft model: a multi-dynamic approach for advanced pharmacokinetic evaluation, studies on the thermal sensitivity of lung cancer cells exposed to an alternating magnetic field and magnesium-doped maghemite nanoparticles.

Magnetic fluid hyperthermia (MFH) represents a promising therapeutic strategy in cancer utilizing the heating capabilities of magnetic nanoparticles when exposed to an alternating magnetic field (AMF). Because...

pH-sensitive polymeric micelles enhance the co-delivery of doxorubicin and docetaxel: an emerging modality for treating breast cancer

Designing and preparing a co-delivery system based on polymeric micelles have attracted in recent years. Co-delivery of anti-cancer agents within pH-sensitive polymeric micelles could provide superior advantag...

Resveratrol-based nano-formulations as an emerging therapeutic strategy for ovarian carcinoma: autophagy stimulation and SIRT-1/Beclin/MMP-9/P53/AKT signaling

Resveratrol (RVS) is a stilbene derivative polyphenolic compound extensively recognized for its anti-inflammatory, antioxidant and anti-aging properties, along with its enormous promise in carcinoma treatment....

Extracellular vesicle miRNAs for predicting the efficacy of late-line treatment with anlotinib in patients with lung adenocarcinoma

Anlotinib is a targeted therapy indicated for some malignancies, including advanced non-small cell lung cancer (NSCLC). However, noninvasive biomarkers for identifying patients who will benefit from this disea...

Biocompatible PLGA-PCL nanobeads for efficient delivery of curcumin to lung cancer

Lung cancer has been mentioned as the first and second most prevalent cancer among males and females worldwide, respectively since conventional approaches do not have enough efficiency in its suppression. Ther...

Delivery of letrozole-encapsulated niosomes via a 3D bioprinting gelatin–alginate scaffold for potential breast cancer treatment

3D printing technology is a powerful tool in scaffold engineering for biomedical applications, especially in anticancer activities and drug delivery. The present study developed a 3D-printed gelatin–alginate s...

Correction: HepG2 exosomes coated luteolin nanoparticles remodeling hepatic stellate cells and combination with sorafenib for the treatment of hepatocellular carcinoma

The original article was published in Cancer Nanotechnology 2024 15 :15

Correction: Carboxymethyl-sagocellulose-stabilized Fe 3 O 4 nanoparticles with 5-fuorouracil as photothermal agents for tumor ablation

The original article was published in Cancer Nanotechnology 2024 15 :18

Direct profiling of breast cancer-derived extracellular vesicles using Pd-perovskite electrochemical biosensing platform

Extracellular vesicles (EVs) harbor several signaling molecules to maintain intercellular communication. Based on the exosomal cargo type, metabolic, genomic, and proteomic status of parent cells can be invest...

A novel PH1/pE27HGFK1 nanoparticles for orthotopic glioblastoma therapy

The therapeutic resistance to ionizing radiation (IR) and angiogenesis inhibitors is a great challenge for clinicians in the treatment of glioblastoma, which is associated with Hepatocyte growth factor (HGF)/M...

An intelligent and self-assembled nanoscale metal organic framework ( 99m TC-DOX loaded Fe 3 O 4 @Fe III -tannic acid) for tumor targeted chemo/chemodynamic theranostics

Recent advances in clinical transformation research have focused on chemodynamic theranostics as an emerging strategy for tackling cancer. Nevertheless, its effectiveness is hampered by the tumor's glutathione...

Black TiO 2 -based nanoparticles as Toll-like receptor stimulator delivery system for enhanced photothermal-immunotherapy of pancreatic cancer

The tumor-specific immune responses, essential for removing residual lesions and preventing tumor metastases, can be stimulated by tumor-associated antigens (TAAs) released following photothermal therapy (PTT)...

Development of a novel nanoformulation based on aloe vera-derived carbon quantum dot and chromium-doped alumina nanoparticle (Al 2 O 3 :Cr@Cdot NPs): evaluating the anticancer and antimicrobial activities of nanoparticles in photodynamic therapy

The objective of this study was to synthesize a novel antibacterial and anticancer nanoformulation using aloe vera-derived carbon quantum dots (Cdot) and chromium-doped alumina nanoparticles (Al 2 O 3 :Cr/Cdot NPs) v...

As1411-modified liposomes to enhance drug utilization and augment the anti-tumor efficacy

The utilization of liposomes in drug delivery has garnered significant attention due to their efficient drug loading capacity and excellent biocompatibility, rendering them a promising platform for tumor thera...

The research trends and future prospects of nanomaterials in breast cancer

Breast cancer is the most common cause of cancer-related deaths among women globally and the most deadly illness for them. New advances in nanotechnology have led to the development of strategies intended to t...

Nanoparticle delivery of si-Notch1 modulates metabolic reprogramming to affect 5-FU resistance and cell pyroptosis in colorectal cancer

Nanocarrier delivery of small interfering RNAs (siRNAs) to silence cancer-associated genes is a promising method for cancer treatment. Here, we explored the role and mechanisms of PLAG NPs-delivered si-Notch1 ...

Advancing colorectal cancer therapy with biosynthesized cobalt oxide nanoparticles: a study on their antioxidant, antibacterial, and anticancer efficacy

Colorectal cancer (CRC) ranks as the third most common cancer globally and the second leading cause of cancer-related mortality. Traditional chemotherapy, while effective, often results in significant side eff...

Hypobaric hypoxia exposure regulates tissue distribution of nanomedicine for enhanced cancer therapy

Effective drug delivery of nanomedicines to targeted sites remains challenging. Given that hypobaric hypoxia and hyperbaric oxygen exposure can significantly change pharmacokinetics of drugs, it is interesting...

A nano-cocktail of the PARP inhibitor talazoparib and CDK inhibitor dinaciclib for the treatment of triple negative breast cancer

The addition of the cyclin dependent kinase inhibitor (CDKi) dinaciclib to Poly-(ADP-ribose) polymerase inhibitor (PARPi) therapy is a strategy to overcome resistance to PARPi in tumors that exhibit homologous...

Mild hyperthermia via gold nanoparticles and visible light irradiation for enhanced siRNA and ASO delivery in 2D and 3D tumour spheroids

The delivery of therapeutic nucleic acids, such as small interfering RNA (siRNA) and antisense oligonucleotides (ASO) into cells, is widely used in gene therapy. Gold nanoparticles (AuNPs) have proved to be ef...

Carboxymethyl-sagocellulose-stabilized Fe 3 O 4 nanoparticles with 5-fluorouracil as photothermal agents for tumor ablation

There is a continuous growth of interest in the development of nano-drug delivery systems that could combine therapy and diagnosis of cancer.

The Correction to this article has been published in Cancer Nanotechnology 2024 15 :31

Antitumor efficiency and photostability of newly green synthesized silver/graphene oxide nanocomposite on different cancer cell lines

It is crucial to enhance new compounds for the treatment of most malignancies, and graphene oxide/silver nanocomposite (GO/Ag NC) has been paying attention to biomedical applications such as malignancies. In t...

Optimization and characterization of quercetin-loaded solid lipid nanoparticles for biomedical application in colorectal cancer

Colorectal cancer (CRC) is a type of cancer that affects the colon or rectum and occurs in individuals over the age of 50, although it can affect people of all ages. Quercetin is a flavonoid, which is a type o...

HepG2 exosomes coated luteolin nanoparticles remodeling hepatic stellate cells and combination with sorafenib for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and recurrence rate. The efficacy of the first-line drug sorafenib is impeded by drug resistance, which is closely related to acti...

The Correction to this article has been published in Cancer Nanotechnology 2024 15 :32

Folic acid-functionalized PEGylated niosomes co-encapsulated cisplatin and doxoribicin exhibit enhanced anticancer efficacy

The medical field is faced with the difficult task of developing a new approach to curing cancer, which is prevalent in organs such as the breast and ovaries and has a high mortality rate. Since chemotherapy i...

Investigation of mitochondria-dependent apoptosis pathway and lipid peroxidation level induced by biosynthesized silver nanoparticles: caspase-3 activation, BAK1/BCLx regulation and malondialdehyde production

Nowadays, silver nanoparticles (AgNPs) have attracted the attention of many researchers due to their special physical, chemical, and biological properties. There is strong evidence that biogenic AgNPs can act ...

Opportunities and challenges of indocyanine green in gastrointestinal cancers for intraoperative and nano-medicine application

The morbidity and mortality of gastrointestinal tumours remain high worldwide. Surgical resection is currently the most critical radical therapeutic schedule, while postoperative complications and sentinel lym...

The effect of doxorubicin curcumin co-loaded lipid nanoparticles and doxorubicin on osteosarcoma before surgery

The research aims to observe the difference in the effect of preoperative doxorubicin curcumin co-loaded lipid nanoparticles (DOX+CUR LPNs) and doxorubicin (VAD) in the treatment of osteosarcoma.

Polymer lipid hybrid nanoparticles encapsulated with Emodin combined with DOX reverse multidrug resistance of breast cancer via IL-6/JAK2/STAT3 signaling pathway

Multidrug resistance (MDR) is one of the main reasons affecting the efficacy of chemotherapy in breast cancer (BC). Our previous studies constructed polymer lipid hybrid nanoparticles encapsulated with Emodin ...

Mesoporous silica nanotechnology: promising advances in augmenting cancer theranostics

Owing to unique facets, such as large surface area, tunable synthesis parameters, and ease of functionalization, mesoporous silica nanoparticles (MSNs) have transpired as a worthwhile platform for cancer thera...

Novel nanoparticle CS-C 60 -Fe 3 O 4 magnetically induces tissue-specific aggregation and enhances thermal ablation of hepatocellular carcinoma

Metallofullerenes are an important type of metallic nanomaterial with promising applications in several medical fields. Thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), i...

Designing nanostructured lipid carriers modified with folate-conjugated chitosan for targeted delivery of osthole to HT-29 colon cancer cells: investigation of anticancer, antioxidant, and antibacterial activities

The present study proposed to design nanostructured lipid carriers (NLC) coated with chitosan (CS) conjugated folate (FA) for the targeted delivery of Osthole (OST) to the HT-29 colon cancer cell line and impr...

Dual-targeting nanomedicine achieves synergistic multimodal therapy for tumor

The poor targeting delivery efficiency and limited efficacy of single therapeutic approach have consistently posed significant challenges in tumor management.

Anticancer platinum-drug delivered by mesenchymal stromal cells improves its activity on glioblastoma

Glioblastoma multiforme (GBM) is nowadays the most aggressive tumor affecting brain in adults with a very poor prognosis due to the limited therapies and the systemic cytotoxicity. Among the different new drug...

SiO 2 –alginate–melittin nano-conjugates suppress the proliferation of ovarian cancer cells: a controlled release approach leveraging alginate lyase

Ovarian cancer treatment is challenged by resistance and off-target effects. Melittin shows promise against cancer but is limited by its instability and harmful cellular interactions. Our study introduces SiO2...

Novel nanotherapeutics for cancer immunotherapy by albumin nanoparticles functionalized with PD-1 and PD-L1 aptamers

PD-1/PD-L1 blockade plays a crucial role in cancer immunotherapy. Exploration of new technologies to further enhance the efficacy of PD-1/PD-L1 blockade is therefore of potential medical importance. Nanotherap...

Synthesis and characterization of silver nanoparticles loaded with carboplatin as a potential antimicrobial and cancer therapy

In recent studies with silver nanoparticles, it has been reported that the use of nanoparticles in carrier drug systems increases tumor suppression and reduces drug-related side effects. At the same time, the ...

Mesothelin-targeted MRI for assessing migration, invasion, and prognosis in malignant pleural mesothelioma

Mesothelin (MSLN) has been implicated in cancer migration, invasion, and prognosis, making it a potential tumor marker. However, the precise role of MSLN in the migration and invasion of malignant pleural meso...

Publisher Correction: Green adeptness in synthesis of non-toxic copper and cobalt oxide nanocomposites with multifaceted bioactivities

The original article was published in Cancer Nanotechnology 2023 14 :79

CD44-specific short peptide A6 boosts cellular uptake and anticancer efficacy of PEGylated liposomal doxorubicin in vitro and in vivo

Although liposomes have improved patient safety and the pharmacokinetic profile of free drugs, their therapeutic efficacy has only shown marginal improvement. The incorporation of active-targeted ligands to en...

Enhanced cancer immunotherapy through synergistic ferroptosis and immune checkpoint blockade using cell membrane-coated nanoparticles

Immune checkpoint blockade (ICB) has achieved unprecedented success in inhibiting the progression and metastasis of many cancers. However, ICB regents as a single treatment have a relatively low overall respon...

Application of tumor microparticles in tumor prevention and treatment

Tumor microparticles (T-MPs) are vesicles released from tumor cells when they receive apoptotic or stimuli signals. T-MPs, which contain some proteins, lipids and nucleic acids from tumor cells, contribute to ...

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Cancer Nanotechnology

ISSN: 1868-6966

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Lattice therapy can help target tumors

Rio grande valley, texas news station highlights uc research.

Rio Grande Valley, Texas news station KRGV-TV highlighted University of Cincinnati Cancer Center researcher Andrew Frankart's new trial testing lattice therapy to provide more targeted radiation for patients with large tumors.

Lattice therapy is a technique where certain parts of tumors are preferentially targeted with higher doses of radiation compared to other areas. 

"Right now, with radiation, we're more restricted to moderate doses that can help relieve symptoms and provide a temporary effect, but may not be sufficient dosing to provide a lasting impact or to control the tumor itself," Frankart, MD, a Cancer Center physician researcher and assistant professor of radiation oncology in UC’s College of Medicine, told KRGV.  "The difference with lattice therapy is it's still using that arc to generate a plan, but we're purposefully making spheres or circles of higher dose within the target."

A five-year, $729,000 American Cancer Society/American Society for Radiation Oncology Clinician Scientist Development Grant is supporting the translation of Frankart’s initial findings into clinical practice through the clinical trial, which is expected to enroll 37 adult patients and analyze the underlying biology of tumor and immune responses to lattice therapy radiation.  

“We’re focusing on patients who have large or bulky tumors. The approach is more based upon where it’s located and how large it is, and those are things that have previously prevented radiation from being as effective,” Frankart said. “Using this new approach to overcome some of those barriers hopefully means it can benefit more patients because we’re broadly including multiple disease sites.” 

Read or watch the KRGV-TV story.

Read more about the trial.

Featured photo at top of Frankart in a radiation treatment room. Photo/Andrew Higley/UC Marketing + Brand.

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