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AACR Cancer Progress Report Details Exciting Advances in Cancer Research and Treatment

Report includes call to action outlining steps congress must take to maintain momentum against cancer for all patients.

PHILADELPHIA – Today, the American Association for Cancer Research (AACR) released the 13th edition of its annual Cancer Progress Report , which chronicles how basic, translational, and clinical cancer research and cancer-related population sciences—primarily supported by federal investments in the National Institutes of Health (NIH) and the National Cancer Institute (NCI)—remain vitally important to improving health and saving lives.

In addition to providing the latest statistics on cancer incidence, mortality, and survivorship, the AACR Cancer Progress Report 2023 offers detailed updates and important context regarding the latest research in cancer etiology, early detection, diagnosis, treatment, prevention, and survivorship. Throughout the report, the personal stories of patients who have benefited from innovative, recently approved anticancer therapeutics highlight the real-world impact of cancer research.

This comprehensive report also features a spotlight on cancer immunotherapy and addresses persistent challenges in cancer research, including cancer disparities, slow progress against certain types of cancer, and the physical, psychosocial, and financial hardships faced by cancer patients, survivors, and their caregivers. A closing call to action outlines steps Congress and other stakeholders must take to ensure that the U.S. maintains its momentum against cancer for the benefit of all patients.

“The advances in cancer research, particularly in the last two decades, have been breathtaking,” said AACR President Philip Greenberg, MD, FAACR, faculty member at Fred Hutchinson Cancer Center. “We are in an era of unparalleled opportunity to make even more breakthroughs for patients. For the cancer research community to achieve these breakthroughs, however, our representatives in Congress must continue to prioritize funding for biomedical research, from basic research to clinical trials. Through the AACR Cancer Progress Report 2023 , we are sharing with the public and policy makers the progress that has been made, how that progress has been delivered to patients, how it’s changed people’s lives, and the unparalleled opportunities that now exist from scientific and technologic advances, so they understand how crucial it is that we maintain this momentum through continued support of NIH and NCI.”

PROMISING TRENDS AND ADVANCES IN CANCER CARE

The medical research community—including researchers in academia and industry, physician-scientists, patient advocates, regulators, and many other stakeholders—has maintained impressive momentum against cancer in recent years. As outlined in the AACR Cancer Progress Report 2023 :

• A new gene therapy-based immunotherapeutic for certain patients with bladder cancer
• A first-in-class antibody drug conjugate for patients with ovarian cancer
• Four new T-cell engaging bispecific antibodies for a range of hematologic malignancies
• The first approval of an immune checkpoint inhibitor for pediatric and adult patients with a rare form of sarcoma
• Due in large part to advances in prevention, early detection, and treatment, the age-adjusted overall cancer death rate in the U.S. fell by 33% between 1991 and 2020— an estimated 3.8 million cancer deaths averted .
• Breast cancer mortality declined by 43% between 1989 and 2020 , leading to an estimated 460,000 fewer breast cancer deaths.
• The decrease in lung cancer mortality has accelerated from 0.9% a year between 1995 and 2005 to nearly 5% a year between 2014 and 2020. This rapid decline is the result of a steep reduction in the U.S. smoking rate as well as the development of numerous highly effective molecularly targeted therapeutics and immunotherapeutics.
• More and better treatment options have led to notable progress against many pediatric cancers as well. Among children (14 and younger) and adolescents (15-19), overall cancer death rates declined by 70% and 64%, respectively, between 1970 and 2020.

THE IMMUNOTHERAPY REVOLUTION

Immunotherapy has revolutionized cancer care. Breakthroughs in this field have contributed to much of the progress noted above, such as declines in the death rates for previously intractable cancers like advanced lung cancer and melanoma. The AACR Cancer Progress Report 2023 contains a spotlight on the history of cancer immunotherapy, the current state of this treatment modality, and the immense promise of the next generation of immunotherapeutics. Highlights include:

• Since 2011, the FDA has approved 11 immune checkpoint inhibitors , which release “brakes” on the surface of certain immune cells—called T cells—so that the T cells are able to destroy cancer cells. Many of these drugs are approved for more than one type of cancer, making immune checkpoint inhibitors a treatment option for 20 cancer types and any tumor with certain specific molecular characteristics.
• Since 2017, the FDA has approved six CAR T-cell therapies to treat a range of hematologic malignancies. CAR T-cell therapy is a type of adoptive cell therapy, which is designed to dramatically increase the number of cancer-killing immune cells a patient has.
• The field is expanding in exciting ways, with researchers combining the power of other cells in the immune system with recent advances in gene editing to develop more personalized and effective versions of adoptive cell therapy for treatment of solid tumors; developing mRNA-based vaccines and therapeutics to treat cancer; and targeting the gut microbiome to increase the efficacy of cancer immunotherapy, among many other innovative approaches.

DESPITE PROGRESS, CHALLENGES PERSIST

Despite the extraordinary scientific progress against cancer in recent years, this complex disease remains a significant threat to human health around the world. In the U.S., it is estimated that nearly 2 million new cases of cancer will be diagnosed and more than 609,000 people will die from the disease in 2023.

Indeed, cancer research and patient care face numerous challenges, as outlined in the AACR Cancer Progress Report 2023 :

• Cancer disparities are a pervasive public health problem, with racial and ethnic minorities and other medically underserved U.S. populations shouldering a disproportionally higher burden of cancer. While advances have been made in identifying, understanding, and addressing some of these disparities, more research and policy solutions are urgently needed to ensure equitable progress against cancer.
• There has been uneven progress against different cancer types. Few treatment options exist for patients diagnosed with pancreatic cancer or glioblastoma, for example, and 5-year relative survival rates for these cancers are extremely low.
• Incidence rates for some cancers are increasing, including for early-onset colorectal cancer, pancreatic cancer, and uterine cancer, in part due to the rising rate of obesity.
• Financial toxicity is widespread, exacerbated by the rising cost of cancer care. In 2019, U.S. cancer patients paid an estimated $16.2 billion in out-of-pocket cancer care costs and lost an additional $5 billion in “time costs.”

FEDERAL FUNDING ESSENTIAL FOR CONTINUED PROGRESS

To confront these and other challenges, the AACR Cancer Progress Report 2023 calls on Congress to support robust, sustained, and predictable annual funding growth for NIH and NCI by providing increases of at least $3.465 billion and $2.6 billion, respectively, in their fiscal year 2024 base budgets. This funding is crucial to continued progress for patients. From 2010 to 2019, NIH funding contributed to the development of 354 out of 356 new drugs, including many cancer drugs, approved by the FDA.

The AACR also urges Congress to:

• Provide $1.7 billion in dedicated funding for Cancer Moonshot activities in FY 2024 across NCI, FDA, and Centers for Disease Control and Prevention (CDC) with the assurance that Moonshot funding will supplement rather than supplant NIH funding in FY 2024.
• Appropriate at least $472.4 million in FY 2024 appropriations for the CDC Division of Cancer Prevention to support comprehensive cancer control, central cancer registries, and screening and awareness programs for specific cancers.
• Allocate $50 million in funding for the Oncology Center of Excellence at FDA in FY 2024 to allow regulators with the capable staff and necessary tools to conduct expedited review of cancer-related medical products.

“We are proud to release the 13 th annual AACR Cancer Progress Report ,” said AACR CEO Margaret Foti, PhD, MD (hc). “It is our hope that this comprehensive resource will help to increase knowledge about the myriad diseases we call cancer as well as the innovative research that is improving and extending lives. The findings in this report, along with the personal stories of the featured patients, underscore the enormous impact that robust, sustained, and predictable funding for cancer research has had on Americans’ health, and why that support must continue.”

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Explore  CRI’s 2023 Cancer Research Impact

Immune to Cancer: The CRI Blog

How CRI’s Immunotherapy Breakthroughs and Research are Shaping Cancer Treatment and Prevention

Today, cancer immunotherapy is the most forward-thinking and innovative form of cancer treatment for patients. Cancer immunotherapy is especially effective with treating melanoma, lung, breast, and several other types of cancer. When possible, however, there is a preferable option compared to treatment: the prevention of cancer entirely.

Want to do something big for cancer immunotherapy research? Make a donation today to the Cancer Research Institute .

CRI scientists are committed to groundbreaking cancer immunotherapy research that can benefit the lives of patients and potentially save lives. In addition to research regarding treating existing cancers, some CRI scientists are also working on forward-thinking research that can address cancer prevention and attack cancer at its roots.

CRI Scientists’ Innovative Work and Perspectives on Cancer Treatment and Prevention

1. Cancer Vaccine Discoveries

Elizabeth Jaffee, MD , deputy director of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and CRI Scientific Advisory Council associate director, serves on the panel for President Joe Biden’s Cancer Moonshot Initiative . Additionally, Dr. Jaffee’s research focuses on novel cancer vaccines, and she has patents for six of them.  Dr. Jaffee foresaw the immense potential of cancer vaccines long before others did. At the 2023 CRI Patient Immunotherapy Summit , she succinctly outlined the transformative power of these vaccines.

“Vaccines are the biggest success story of the 20 th century other than penicillin,” Dr. Jaffee says. “We have suggested developing new technologies and new computational approaches that can take all of the new data we are generating and put it into a framework, biologically, that tells us which signals a tumor is sending out to cells around it to cause it to protect the tumor. Through that information we can develop drugs that can intercept those signals. We can now take vaccines, combine them with drugs, and we can make a difference. We are seeing vaccines close to approval for cancers like melanoma. We are going to see this happening more and more over the next five years.”

2. Measuring Immunotherapy Response in a Single Drop of Blood

  Valsamo (Elsa) Anagnostou, MD, PhD , director of the thoracic oncology biorepository at Johns Hopkins, leader of Precision Oncology Analytics, co-leader of the Johns Hopkins Molecular Tumor Board, co-director of the Lung Cancer Precision Medicine Center of Excellence, CRI Torrey Coast Foundation GEMINI CLIP Investigator, and CRI Clinical Accelerator is at the forefront of leveraging cutting-edge technologies to advance diagnosis and therapy response. Her pioneering work has unleashed the power of liquid biopsies to test ctDNA (circulating tumor DNA) in patient blood, revolutionizing our ability to gauge patient responses to treatment.  Liquid biopsies involve drawing small samples of blood from patients for testing. “ctDNA response is particularly informative to understand the complexity of stable disease on imaging, which represents a sizable fraction of patients in whom imaging fails to timely and accurately detect the magnitude of therapeutic response,” Dr. Anagnostou says. “ctDNA response correlated with tumor size seen on imaging, which is the gold standard for monitoring response to cancer treatments and seemed to be better correlated with survival.”

Liquid biopsies could be the first step in preventing excessive follow-up procedures and scans. This is a technology that can further be developed to test for markers in blood that can indicate presence of undetectable tumors or the presence of cancer cells even before they become large enough tumors to be detected using traditional scans.

3. The Tumor Microenvironment Holds the Answer to Cancer

Max Krummel, PhD, Robert E. Smith Endowed Chair in Experimental Pathology at the University of California San Francisco (UCSF), Professor, Department of Pathology at UCSF, and former CRI Investigator Award recipient, emphasizes the need to broaden our perspective on cancer prevention beyond the current focus on boosting T cell responses through checkpoint blockade. While acknowledging the significance of enhancing T cell activity, Dr. Krummel sees an equally promising avenue in understanding and targeting the tumor microenvironment (TME). The TME is comprised of the non-cancerous cells, blood vessels, and molecules that surround and sustain a tumor cell. He highlights, “We have started to think about the fundamental biology of the tumor and how to target [that].” This shift in focus towards comprehending the intricacies of the tumor microenvironment underscores the importance of exploring diverse approaches in our efforts to combat cancer effectively.

In the U.S. alone, about 600,000 people die from cancer annually. While treatment methods have improved in recent years, particularly with immunotherapy, there is no silver bullet for cancer prevention, there are several measures people can take to try and safeguard against a potential cancer diagnosis (via the Mayo Clinic).

Measures That can Help Prevent Cancer

1. Screen Early

Different populations are at greater risk of diagnosis depending on the type of cancer. For former and current smokers, screening against lung cancer is critical. Another example is that for women between 40-75 years old, having a mammogram every two years is greatly encouraged to guard against breast cancer .

Additionally, there are also tests that can detect specific cancer-related mutations that are routinely performed to determine if someone is at risk for cancer.

2. Limit Exposure to Harmful UV Rays

Limiting the amount of time your skin is exposed to the sun and avoiding tanning booths is a good way to safeguard against skin cancer.   If you are going to be in the sun, applying sunscreen and covering your skin as best you can be good safety measures.

3. Consider Cancer Vaccines

There are currently four distinct preventative cancer vaccines for HPV and HBV-associated cancers that have been approved by the FDA. Viral infections have proven responsible for several cancers, and preventative cancer vaccines are an important tool to help thwart off cancer before it can develop.

Additionally, there are two approved therapeutic cancer vaccines for bladder and prostate cancers. These vaccines help the immune system identify cancer cells so they can be eliminated.

4. Maintain a Healthy Diet

Certain dietary measures, such as reducing one’s intake of red meat, can help reduce an individual’s risk of a cancer diagnosis . A healthy diet is one that is focused on fruits and vegetables, while avoiding refined sugars and excess animal fat.

Between new developments in cancer immunotherapy on the horizon and greater education of the public regarding preventative measures, there is potential for a greater collective focus on cancer prevention, and therefore, a world immune to cancer.

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New cancer research impacting treatment, prevention, early diagnosis, and quality of life to be presented at the 2024 asco annual meeting in chicago.

ALEXANDRIA, Va. – The global oncology community will gather in Chicago to share and discuss the latest clinical cancer research impacting patient care at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Treatment advances involving targeted therapies, immunotherapy, and new uses of technology, as well as research on improving patient quality of life and outcomes are among the topics that will be highlighted in the meeting’s official Press Program.  

The 2024 ASCO Annual Meeting will take place May 31-June 4 in Chicago and online. The theme of this year’s conference is The Art and Science of Cancer Care: From Comfort to Cure.  

This year, ASCO received a record number of abstract submissions and as a result more than 5,000 abstracts will be presented or published as part of the 2024 ASCO Annual Meeting. ASCO will publish the regular abstracts on Thursday, May 23, at 5:00 PM (ET) on asco.org/abstracts . Late-Breaking Abstracts (LBAs), including Plenary abstracts, will be released at 7:00 AM (CT)/8:00 AM (ET) on their day of scientific presentation at the Meeting. The complete embargo schedule is available online . 

EMBARGOED PRE-MEETING PRESS BRIEFING (VIRTUAL EVENT) – Thursday, May 23, 12:00-1:30 PM (ET)

In advance of the release of regular abstracts on May 23, an embargoed, virtual press briefing for credentialed media will be held earlier the same day and will highlight four abstracts. The embargo will lift on May 23 at 5:00 PM (ET) for the following studies:

• Using artificial intelligence to re-engage communities of color who have missed colonoscopy appointments (Abstract 100)  
• A prospective study examining long-term fertility outcomes among younger breast cancer survivors. (Abstract 1518)
• Lessons from a prospective trial examining treatment-induced neuropathy in Black women with breast cancer (Abstract 503)
• Impact of HPV vaccination on cancer rates beyond cervical cancer, among both men and women (Abstract 10507)  

EMBARGOED PRE-MEETING PRESS BRIEFING (VIRTUAL EVENT) – Wednesday, May 29, 9:30-11:00 AM (ET)

Several Late-Breaking Abstracts (LBAs) being presented on Friday, May 31 and Saturday, June 1 at the meeting, will be discussed in an embargoed, virtual press briefing for credentialed media on May 29:

• Five-year survival and safety outcomes from the phase III CROWN study comparing lorlatinib to crizotinib in treatment-naïve patients with advanced  ALK + non-small cell lung cancer. (Abstract LBA8503)   Embargo lifts Friday, May 31 at 7:00 AM (CT)/8:00 AM (ET) 
• The primary results from the ASC4FIRST study, a randomized phase III trial looking at asciminib compared to investigator-selected tyrosine kinase inhibitors in newly diagnosed patients with chronic myeloid leukemia. (Abstract LBA6500)   Embargo lifts Friday, May 31 at 7:00 AM (CT)/8:00 AM (ET)
• Results from the phase III GHSG HD21 study, examining tolerability and efficacy of BrECADD compared to BEACOPP in advanced stage classical Hodgkin lymphoma. (Abstract LBA7000) Embargo lifts Saturday, June 1 at 7:00 AM (CT)/8:00 AM (ET) 

RESEARCH TO BE RELEASED DURING THE ANNUAL MEETING  

During the Annual Meeting, two press briefings will be held on Saturday, June 1: one from 8:00-9:15 AM (CT) highlighting research from ASCO’s Plenary Session and one from 12:30-1:30 PM (CT) highlighting additional LBAs that will be presented during the meeting. The press briefings will be held in person and livestreamed for credentialed reporters covering the meeting remotely.

LBAs that will be featured in these press briefings include:

• The prospective phase III ESOPEC trial comparing perioperative chemotherapy to neoadjuvant chemoradiation in patients with esophageal cancer. (Plenary, Abstract LBA1)   Embargo lifts Sunday, June 2 at 7:00 AM (CT)/8:00 AM (ET)  
• The phase III NADINA trial studying neoadjuvant nivolumab plus ipilimumab compared to adjuvant nivolumab in melanoma. (Plenary, Abstract LBA2)   Embargo lifts Sunday, June 2 at 7:00 AM (CT)/8:00 AM (ET) 
• Trial evaluating the effectiveness of early palliative care delivered via telehealth compared to in-person for patients with advanced lung cancer. (Plenary, Abstract LBA3)   Embargo lifts Sunday, June 2 at 7:00 AM (CT)/8:00 AM (ET) 
• Primary results of the phase 3 LAURA study examining osimertinib after chemoradiotherapy in patients with unresectable stage III epidermal growth factor receptor-mutated non-small cell lung cancer. (Plenary, Abstract LBA4) Embargo lifts Sunday, June 2 at 7:00 AM (CT)/8:00 AM (ET)   
• The phase III ADRIATIC study evaluating durvalumab with or without tremelimumab in patients with limited-stage small-cell lung cancer. (Plenary, LBA5) Embargo lifts Sunday, June 2 at 7:00 AM (CT)/8:00 AM (ET)   
• The randomized phase III DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone compared to pomalidomide plus bortezomib and dexamethasone in relapsed or refractory multiple myeloma. (Abstract LBA105) Embargo lifts Sunday, June 2 at 7:00 AM (CT)/8:00 AM (ET)   
• The CARACO phase III randomized trial, studying the omission of lymphadenectomy in patients with advanced ovarian cancer treated with cytoreductive surgery after neoadjuvant chemotherapy. (Abstract LBA5505)   Embargo lifts Sunday, June 2 at 7:00 AM (CT)/8:00 AM (ET) 

All press briefings will also be recorded and made available to credentialed reporters in ASCO’s Media Headquarters.

ADDITIONAL STUDIES OF NOTE

The following studies will be included in the official ASCO Tip Sheet, a brief summary of additional noteworthy research. The Tip Sheet will be sent to credentialed reporters ahead of the meeting and will include additional comments from the lead authors and ASCO experts.

The embargo will lift Thursday, May 23 at 5:00 PM (ET) for the following studies:  

• Addition of the MUC-1 vaccine tecemotide to neoadjuvant systemic therapy for patients with early breast cancer: Survival results from the prospective randomized ABCSG 34 trial. (Abstract 587)
• Trends in human papilloma virus vaccination uptake by sex and race/ethnicity among US adolescents and young adults, 2011-2020. (Abstract 10519)
• Phase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with newly diagnosed multiple myeloma (IMROZ). (Abstract 7500)
• Chemotherapy and liver transplantation versus chemotherapy alone in patients with definitively unresectable colorectal liver metastases: A prospective multicentric randomized trial (TRANSMET). (Abstract 3500)
• A phase 1 study of JNJ-69086420 (JNJ-6420), an actinium-225 (225Ac) -labeled antibody targeting human kallikrein 2 (hK2), for metastatic castration-resistant prostate cancer (mCRPC). (Abstract 5010).
• Evolution of tisagenlecleucel use for the treatment of pediatric and young adult relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL): Center for International Blood & Marrow Transplant Research (CIBMTR) registry results. (Abstract 10016).
• Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer: Overall survival and updated 5-year results from the randomized DYNAMIC trial. (Abstract 108).
• The potential role of serial circulating tumor DNA (ctDNA) testing after upfront surgery to guide adjuvant chemotherapy for early stage pancreatic cancer: The AGITG DYNAMIC-Pancreas trial. (Abstract 107).
• Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): Results from the phase III OptiTROP-Breast01 study. (Abstract 104)
• Survival outcomes associated with first-line PCV or temozolomide in combination with radiotherapy in IDH-mutant 1p/19q-codeleted grade 3 oligodendroglioma. (Abstract 2004)
• First-line inavolisib/placebo + palbociclib + fulvestrant (Inavo/Pbo+Palbo+Fulv) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2‑negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 Phase III randomized trial additional analyses. (Abstract 1003).
• Circulating kidney injury molecule-1 (KIM-1) biomarker analysis in IMmotion010: A randomized phase 3 study of adjuvant (adj) atezolizumab (atezo) vs placebo (pbo) in patients (pts) with renal cell carcinoma (RCC) at increased risk of recurrence after resection. (Abstract 4506)
• Multi-site randomized trial of stepped palliative care (PC) for patients with advanced lung cancer. ( Abstract 12000)
• A randomized phase II study of gemcitabine and nab-paclitaxel compared with 5-fluorouracil, leucovorin, and liposomal irinotecan in older patients with treatment-naïve metastatic pancreatic cancer (GIANT): ECOG-ACRIN EA2186. (Abstract 4003)

The embargo will lift Friday, May 31 at 7:00 AM (CT)/8:00 AM (ET) for the following study :

• Subcutaneous amivantamab vs intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results, including overall survival (OS), from the global, phase 3, randomized controlled PALOMA-3 trial.  (Abstract LBA8505)

The embargo will lift Saturday, June 1 at 7:00 AM (CT)/8:00 AM (ET) for the following studies:

• KRYSTAL-12: Phase 3 study of adagrasib versus docetaxel in patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC) harboring a KRAS G12C  mutation. (LBA8509)
• Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial (LBA1001)

The embargo will lift Monday, June 3 at 7:00 AM (CT)/8:00 AM (ET) for the following studies :

• Durable complete responses to PD-1 blockade alone in mismatch repair deficient locally advanced rectal cancer.  (Abstract LBA3512)
• IMpower010: Final disease-free survival (DFS) and second overall survival (OS) interim results after ≥5 years of follow up of a phase III study of adjuvant atezolizumab vs best supportive care in resected stage IB-IIIA non-small cell lung cancer (NSCLC). (LBA8035)

MEDIA RESOURCES  

Media registration : To participate in the Annual Meeting press briefings and/or register to attend the Meeting in person in Chicago, please visit ASCO’s Media Headquarters at https://profile.asco.org/media/workflow . Step-by-step instructions are available online . 

Requests for media credentials must be submitted in Media Headquarters no later than Wednesday, May 15, to participate in the pre-meeting press briefing on May 23. Pre-registration is required for on-site attendance and must also be requested by this date. 

Annual Meeting Media Resource Center : Visit asco.org/AMMRC for press releases, the press briefing schedule, embargo policies, high-resolution photos, and the Virtual Press Room (an online repository of corporate and institutional press materials from third-party organizations).  

About ASCO :  

Founded in 1964, the American Society of Clinical Oncology, Inc. (ASCO®) is committed to the principle that knowledge conquers cancer. Together with the Association for Clinical Oncology, ASCO represents nearly 50,000 oncology professionals who care for people living with cancer. Through research, education, and promotion of high quality, equitable patient care, ASCO works to conquer cancer and create a world where cancer is prevented or cured, and every survivor is healthy. Conquer Cancer, the ASCO Foundation, supports ASCO by funding groundbreaking research and education across cancer’s full continuum. Learn more at  www.ASCO.org , explore patient education resources at  www.Cancer.Net , and follow us on  Facebook ,  Twitter ,  LinkedIn ,  Instagram , and  YouTube .

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Prospects of molecular hydrogen in cancer prevention and treatment

• Open access
• Published: 31 March 2024
• Volume 150 , article number  170 , ( 2024 )

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• Wenchang Zhou 1 , 2 ,
• Jie Zhang 1 , 2 ,
• Wankun Chen 1 , 2 &
• Changhong Miao 1 , 2  

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Gas signaling molecules, including carbon monoxide (CO), nitric oxide (NO), and hydrogen sulfide (H 2 S), have been shown to have cancer therapeutic potential, pointing to a new direction for cancer treatment. In recent years, a series of studies have confirmed that hydrogen (H 2 ), a weakly reductive gas, also has therapeutic effects on various cancers and can mitigate oxidative stress caused by radiation and chemotherapy, reducing tissue damage and immunosuppression to improve prognosis. Meanwhile, H 2 also has immunomodulatory effects, inhibiting T cell exhaustion and enhancing T cell anti-tumor function. It is worth noting that human intestinal flora can produce large amounts of H 2 daily, which becomes a natural barrier to maintaining the body’s resistance to diseases such as tumors. Although the potential anti-tumor mechanisms of H 2 are still to be investigated, previous studies have shown that H 2 can selectively scavenge highly toxic reactive oxygen species (ROS) and inhibit various ROS-dependent signaling pathways in cancer cells, thus inhibiting cancer cell proliferation and metastasis. The ROS scavenging ability of H 2 may also be the underlying mechanism of its immunomodulatory function. In this paper, we review the significance of H 2 produced by intestinal flora on the immune homeostasis of the body, the role of H 2 in cancer therapy and the underlying mechanisms, and the specific application of H 2 to provide new ideas for the comprehensive treatment of cancer patients.

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Avoid common mistakes on your manuscript.

Introduction

According to recent World Health Organization (WHO) statistics (Sung et al. 2021 ; Wen et al. 2021 ; Siegel et al. 2020 ), cancers are the first or second leading cause of death in 112 of 183 countries worldwide, posing a severe threat to human health, and overall the global burden of cancer morbidity and mortality will continue to increase (Wen et al. 2021 ). Currently, surgery is still the primary method to treat solid cancers, combined with radiotherapy and chemotherapy, including a variety of cytotoxic drugs, tyrosine kinase inhibitors, in addition to immunotherapy such as immune checkpoint inhibitors, such as anti-programmed cell death 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibodies (Xu et al. 2018 ). However, these approaches often fail to achieve satisfactory clinical results in cancer treatment (Vasan et al. 2019 ).

Gas signaling molecules are small molecule gases that affect cellular biology by regulating signal transduction, such as nitric oxide (NO) (Tien Vo et al. 2021 ), carbon monoxide (CO) (Oliveira et al. 2018 ), and hydrogen sulfide (H 2 S) (Flannigan and Wallace 2015 ). Studies have confirmed that multiple gas signaling molecules have anti-tumor properties and can be used directly or as products of specific agents for anti-tumor treatment.

Recently, studies have proved H 2 to be another gas signaling molecule showing intriguing potential in cancer therapy (Wu et al. 2019 ; Li et al. 2019 ). Since 1975, when Dole et al. ( 1975 ) found that high concentrations of H 2 could cure squamous cell carcinoma implanted in the skin of mice, numerous laboratory and clinical studies have confirmed that H 2 is effective against various cancers (Wu et al. 2019 ; Li et al. 2019 ; Hirano et al. 2021a ). Furthermore, H 2 effectively synergizes with anti-tumor therapies such as radiotherapy and cytotoxic drugs (Runtuwene et al. 2015 ; Meng et al. 2015 ; Hirano et al. 2021b ), reducing damage to body (Yang et al. 2012 ) and improving patient prognosis.

In a landmark study in 2007 (Ohsawa et al. 2007 ), Oshawa et al. found that H 2 could selectively neutralize highly toxic reactive oxygen species (ROS) (hydroxyl radicals, ·OH, and peroxynitrite, ONOO–) without affecting other physiological ROS. The ROS-scavenging capacity of H 2 is likely to be a critical underlying mechanism for its anti-tumor activity. However, the underlying mechanism of hydrogen in tumor therapy is controversial due to the lack of specific signaling receptors that other gas signaling molecules have. In this review, we first discuss the importance of H 2 metabolism by the intestinal flora under physiological conditions for the homeostasis of the human internal environment. Then we discuss the mechanism of H 2 anti-tumor through its unique antioxidant capacity to provide a comprehensive account of the mechanism of hydrogen action in tumor therapy. At last, we discussed the specific role of different application modalities of H 2 and explored the prospect of hydrogen application in clinical tumor therapy.

Anti-tumor barrier: H 2 produced by intestinal flora

Under normal physiological conditions, adult gut microbiota can produce large amounts of H 2 daily (Mego et al. 2017 ; Carbonero et al. 2012 ), and this H 2 can regulate the balance of intestinal flora and their metabolites, which are essential for immune homeostasis in humans. It demonstrates that H 2 is the body’s natural anti-tumor barrier and provides new strategies for its clinical use.

H 2 metabolism in  intestine

The intestinal hydrogenogenic bacteria mainly use various indigestible carbohydrates as substrates for anaerobic oxidative energy production, including starch, cellulose, and some sugars (Jiang et al. 2020 ). This process can produce large amounts of H 2, which is quickly absorbed and used by hydrogenotrophic bacteria. H 2 participates in this series of reactions as an electron transporter and is a vital energy substance for the survival and proliferation of intestinal flora (Carbonero et al. 2012 ; Greening et al. 2016 ). Most of the H 2 not used by the flora is excreted through respiration and the anus, while the rest can enter the circulation or penetrate the intestinal lumen and peritoneum into the peritoneal cavity (Nishimura et al. 2013 ).

The hydrogenotrophic bacteria mainly include reductive acetate-producing bacteria, sulfate-reducing bacteria (SRB), and methanogenic bacteria, which, respectively, oxidize H 2 to acetate, H 2 S, and CH 4 (Carbonero et al. 2012 ). The H 2 concentration in the intestine not only passively responds to the balance of these florae but also controls the balance of hydrogenogenic and hydrogenotrophic flora by partial pressure of hydrogen (pH 2 ) (Carbonero et al. 2012 ). For example, a study found (Ge et al. 2022 ) that hydrogen-rich water (HRW) supplementation significantly inhibited the expansion of opportunistic pathogenic E. coli and increased intestinal integrity in mice with colitis by modulating intestinal flora H 2 metabolism.

Studies have confirmed that intestinal flora disorders can affect the occurrence and development of cancers in multiple organs throughout the body, including colorectal cancers (Song et al. 2020 ; Helmink et al. 2019 ). Although hydrogenogenic and hydrogenotrophic microbes cover most intestinal flora, the specific morphology and metabolism of the flora contained in them vary greatly and lack proper taxonomy, so there are few articles directly studying the relationship between intestinal H 2 metabolizing and cancers. Several studies investigated the genomic and meta-genomic distribution of hydrogenases, the reversible enzymes that catalyze the oxidation and evolution of H 2 , to understand more about the contribution of H 2 metabolism to gut ecosystems (Greening et al. 2016 ; Peters et al. 2015 ; Suzuki et al. 2018 ). According to the binding metal cofactor, Greening et al. identified 4 groups (22 subgroups) of [NiFe]-hydrogenases, 3 groups (6 isoforms) of [FeFe]-hydrogenases, and a small group of [Fe]-hydrogenases (Greening et al. 2016 ). This hydrogenase diversity supports crucial metabolic pathways of intestinal flora, such as H 2 -based respiration, fermentation, and carbon fixation processes, reflecting the scope of H 2 metabolism in sustaining the growth and survival of microorganisms. Until now, the authors indicated that most related studies focus on only a few branches of the hydrogenase phylogenetic tree and a small fraction of organisms within the universal tree of microorganisms.

However, it is easy to find that H 2 produced by intestinal flora can participate in the regulation of various flora metabolites related to carcinogenesis (Ge et al. 2022 ; Fan and Pedersen 2021 ; Kalantar-Zadeh et al. 2019 ), such as H 2 can scavenge ROS and promote the production of short-chain fatty acids (SCFAs). For example, a study demonstrated that oral administration of HRW in mice could promote the production of SCFAs in cecal contents and circulation by modulating the composition of intestinal flora (Higashimura et al. 2018 ).

In contrast, high SRB and sulfur protein diets are associated with the development of colon cancer (Nguyen et al. 2020 ; Lee et al. 2022 ), which can disrupt cytochrome oxidase, inhibit butyrate utilization, block mucus synthesis, and cause DNA methylation through the production of H 2 S. In addition, excessive H 2 S production by intestinal flora plays an important role in the carcinogenesis and development of intestinal tumors (Ngowi et al. 2021 ; Attene-Ramos et al. 2010 ; Dalal et al. 2021 ). Paradoxically, various sulfur-containing diets have long-proven anti-tumor properties, such as garlic and cruciferous vegetables (Rose et al. 2021 ; Abbaoui et al. 2018 ). We think part of the reason is the balance of SRB with other hydrogen-metabolizing flora in the lumen in those different dietary settings. Moreover, the balance of H 2 and H 2 S metabolized by SRB may be the underlying mechanism (Fig.  1 ).

H 2 metabolism in intestinal flora regulates intestinal health. Hydrogenogens produce H 2 during fermentation in the human colon and result in a rapid increase of pH 2 , which restrict further fermentation. Three groups of hydrogenotrophic (H 2 utilizing) microbes can oxidize H 2 , simultaneously lowering pH 2 and enabling fermentation to continue. H 2 S produced by SRB can damage the intestinal epithelium and induce inflammation and tumorigenesis, while H 2 can antagonize the malignant effects of H 2 S by producing SCFA and scavenging ROS. SCFAs: short-chain fatty acids; SRB: sulfate-reducing bacteria; pH 2 : partial pressure of hydrogen

 H 2 produced by intestinal flora can maitain homeostasis

Intestinal H 2 metabolizing is not only fundamental to gut health but also crucial for redox balance and immune homeostasis in multiple organs (Fig.  2 ).

H 2 produced by intestinal flora maintains multi-system health and immune homeostasis. The hydrogen produced in the intestine can penetrate the abdominal cavity or bloodstream, exerting a protective effect on multiple organs throughout the body. On the other hand, hydrogen is a substrate for SCFA production by intestinal flora. It promotes the production of SCFA, a vital energy substance for intestinal epithelial cells and immune cells, maintaining the integrity of the intestinal barrier and the stability of the systemic immune system. COPD: chronic obstructive pulmonary disease; ARDS: acute respiratory distress syndrome; SCFA: short-chain fatty acid

Studies have shown that H 2 maintains the integrity of the intestinal barrier, reduces intestinal inflammation and damage in rat (Wu et al. 2017 ), and protects ischemia–reperfusion of the brain, lung, liver, and other organs (Dong et al. 2018 ; Fang et al. 2018 ; Sano et al. 2018 ; Ishikawa et al. 2018 ). H 2 is also fundamental to pelvic health and guarantees organ function (Zhang et al. 2021 ). In male and female organs, such as testes and ovaries, after damage leading to dysfunction, H 2 supplementation can effectively reduce oxidative stress and promote recovery of organ function. Although many studies have focused on exogenous H 2 supplementation, H 2 production in the gut is as effective as H 2 inhalation and H 2 oral HRW in raising H 2 levels in the body. For example, the administration of fructose promotes an 11-fold increase in intraperitoneal H 2 concentration and a significant increase in H 2 in the blood system (Nishimura et al. 2013 ).

SCFA is an essential source of energy for intestinal epithelium and multiple immune cells (Yip et al. 2021 ), as well as a communication material between the gut–lung axis and gut–brain axis (Fulling et al. 2019 ) that sustains immune homeostasis throughout the body. H 2 , produced by gut bacteria, is the substrate for SCFAs synthesis and promotes the synthesis of SCFAs. It was found that HRW can increase propionate, butyric acid, and total SCFAs in the gut by regulating gut flora to treat brain diseases such as Parkinsonism (Bordoni et al. 2019 ; Ostojic 2021 ). Diets or medications that promote H 2 production in the gut, such as high-fiber diets and lactose, also promote the production of SCFAs (Chen and Vitetta 2018 ; Zhai et al. 2018 ). A study in mice (Ge et al. 2022 ) suggested that HRW can strengthen the intestinal barrier by regulating specific mucositis-related mucolytic bacteria through the H 2 –H 2 metabolic microbiota–SCFAs axis, ensuring the body’s internal environment.

Anti-tumor effect of H 2 and the underlying mechanism

H 2 anti-tumor and synergistic anti-tumor effects.

Starting with the research by Dole et al. ( 1975 ) that high concentrations of H 2 cured squamous carcinomas grown on mouse skin, several studies have confirmed the anti-tumor effects of H 2 . Wang et al. ( 2018 ) reported that in cells and mice, H 2 inhibited the proliferation, metastasis, and invasion of lung cancer cells and reduced lung cancer volume by inhibiting chromosome stabilization protein 3 (SMC3). A clinical study by Akagi and Baba ( 2019 ) found that inhalation of H 2 for 3 h daily significantly prolonged progression-free survival and overall survival in stage IV colon and rectal patients. A study of inhaled H 2 in 82 cases of intermediate to advanced cancer treatment also confirmed the anti-tumor effect of H 2 (Chen et al. 2020 ).

Chemotherapy and radiotherapy are still the main strategies for cancer treatment. However, these treatment regimens lead to significant oxidative stress and inflammation, causing damage to human organs, and H 2 can be used as an adjuvant regimen to suppress these adverse effects due to its cytoprotective properties, such as antioxidant and anti-inflammatory (Meng et al. 2015 ). Runtuwene et al. ( 2015 ) gave HRW drinking to colorectal cancer-bearing mice treated with 5-fluorouracil intravenously. They found that HRW enhanced apoptosis of cancer cells by causing significant increases in the expression of p-AMPK, apoptosis-inducing factor (AIF), and caspase-3 in non-cancer cells and prolonging the life span of cancer-bearing animals. Cisplatin causes the accumulation of ROS in humans, decreases glutathione activity, and causes increased oxidative stress, while H 2 reverses cisplatin-induced oxidative stress in the body and restores antioxidant enzyme activity (Kikkawa et al. 2014 ). In addition, H 2 reduces cisplatin’s nephrotoxicity without affecting its anti-tumor effect and enhances animal survival in mice experiments. Oral administration of HRW (0.55–0.65 mM, 1.5–2.0 L per day) to patients with hepatocellular carcinoma receiving radiotherapy suppressed the level of oxidative stress in patients and improved their quality of life without affecting the effect of radiotherapy (Nakashima-Kamimura et al. 2009 ). Some studies reported that the administration of inhaled H 2 during radiotherapy treatment reduced the damage to the hematological and immune systems (Hirano et al. 2021b ; Yang et al. 2012 ) and alleviated the growth of radiotherapy-induced thymic lymphoma (Zhao et al. 2011 ).

Although a series of studies have confirmed the anti-tumor effects of H 2 , it is indispensable to understand the underlying mechanisms in depth to support further H 2 application in clinic. H 2 has an extensive range of physiological effects, including anti-oxidative stress, anti-inflammation, and regulation of apoptosis (Li et al. 2019 ). Furthermore, some studies proved that H 2 has an anti-tumor effect by indirectly regulating gene expression (Hirano et al. 2021a ). Through these studies, we believe that the ability of H 2 to selectively scavenge highly toxic ROS may be the core and fundamental mechanism of its anti-tumor effects, so this paper mainly focuses on this point of discussion.

H 2 anti-tumor activity through anti-oxidative stress

Intracellular ROS are mainly derived from catalytic reactions regulated by oxidative phosphorylation (OXPHOS) of the mitochondrial respiratory chain and NADPH oxidase (NOX) in the cytoplasm (Holmstrom and Finkel 2014 ). On the one hand, ROS are extremely oxidative and destructive to biomolecules proteins, phospholipids, and nucleic acids; on the other hand, ROS are key intracellular signaling molecules that can affect cell proliferation and differentiation by regulating various signaling pathways, such as NF-κB and Akt/mTOR (Cheung and Vousden 2022 ; Zhang et al. 2016 ). Under normal physiological conditions, the complete system of antioxidant enzymes in the body keeps the ROS concentration in a precise dynamic balance, including superoxide dismutase (SOD), which converts \({\text{O}}_2^{\cdot -}\) to H 2 O 2 , then glutathione peroxidase (GPx) and catalase (CAT) convert H 2 O 2 to water (Cheung and Vousden 2022 ; Meng et al. 2021 ). However, the body lacks specific scavenging systems for ·OH and ONOO–, and these two ROS are highly cytotoxic and have damaging effects on almost all macromolecules (proteins, nucleic acids, lipids), which can lead to DNA double-strand structure disruption and base pairing damage (Cheung and Vousden 2022 ; Jena 2012 ), resulting in carcinogenesis.

Activation of oncogenes altered mitochondrial function (Ismail et al. 2019 ), and hypoxia collectively contribute to increased ROS production in cancer cells. Unfortunately, the antioxidant enzyme system in tumor cells is often unable to counteract overgenerated ROS, resulting in a high ROS state in the tumor microenvironment (Cheung and Vousden 2022 ; Zhang et al. 2016 ; Liao et al. 2019 ; Hornsveld and Dansen 2016 ). Indeed, cancer cells can not only adapt to a moderately high ROS state but also take advantage of ROS to drive the malignant phenotype. This happens because ROS can enhance NF-κB, Akt/mTOR, Wnt/β-catenin pathways, and oncogenes such as Ras, Bcr/Abl, and c-Myc expression (Cheung and Vousden 2022 ; Liao et al. 2019 ; Hornsveld and Dansen 2016 ; Wojtovich et al. 2019 ), which maintain high-intensity metabolism and proliferation of tumor cells. Furthermore, ROS-dependent signaling pathways can promote cancer invasion and metastasis (Cheung and Vousden 2022 ; Liao et al. 2019 ). However, some reports (Cheung and Vousden 2022 ; Hornsveld and Dansen 2016 ) suggest that persistently elevated ROS in the cancer microenvironment can limit further cancer progression after reaching a certain level. Thus, non-selective antioxidant therapy in cancer treatment may lead to further cancer progression (Meng et al. 2021 ; Sayin et al. 2014 ; Chandel and Tuveson 2014 ). H 2 selectively removes strongly oxidizing without affecting other ROS, making it an ideal therapy antioxidant.

On the one hand, H 2 can inhibit the damage of cellular DNA by ·OH and ONOO– to prevent cancer development; on the other hand, H 2 can remove ROS from cancer cells and inhibit multiple ROS-dependent metabolic signaling pathways to suppress cancer development. Studies have confirmed that H 2 can effectively reduce oxidative stress caused by various pathological conditions, including cancers, and promote the restoration of redox homeostasis (Adzavon et al. 2022 ; Shi et al. 2016 ; Kawai et al. 2012 ).

H 2 can also elevate the expression of some antioxidant enzymes that play a crucial role in regulating redox homeostasis in cancer cells (Li et al. 2019 ; Slezak et al. 2021 ), which exerts anti-tumor effects. Some non-cancer studies proved that H 2 treatment induced a significant increase in the expression of intracellular SOD, GPx, CAT (Zhou et al. 2019 ), and heme oxygenase-1 (HO-1) (Fang et al. 2018 ; Iketani et al. 2017 ), enhancing their potential to eliminate ROS.

H 2 ’s ability to modulate various signaling pathways is another essential mechanism for its antioxidant action, such as Nrf2/ARE and p38/MAPK (Fang et al. 2018 ; Slezak et al. 2021 ; Xie et al. 2020 ). A series of subsequent studies have found that H 2 also maintains redox balance in the body by activating the Keap1-Nrf2-ARE, and Nrf2-HO-1 pathways (Slezak et al. 2021 ; Xie et al. 2020 ; Yu et al. 2019 ; Chen et al. 2015 ), which exerts immunomodulatory, anti-inflammatory, and cancer pro-apoptotic effects. Wang et al. ( 2018 ) found that H 2 inhibited ROS expression and increased SOD, IL-1β, IL-8, IL-13, and tumor necrosis factor-α (TNF-α) expression in lung tissue of cancer-bearing mice. (Fig.  3 ).

Mechanisms of H 2 in anti-oxidative stress. SOD: superoxide dismutase; CAT: catalase; GPx: glutathione peroxidase; HO-1: heme oxygenase 1; MPO: myeloperoxidase; GSS: glutathione synthetase; MAPK: mitogen-activated protein kinase; JNK: c-Jun N-terminal kinase; Nrf2: nuclear factor-erythroid-2-related factor 2; ARE: antioxidant response elements; NF-κB: nuclear factor kappa B; TNF-α: tumor necrosis factor-alpha; ICAM-1: intercellular cell adhesion molecule-1; IFN-γ: interferon-gamma; IL-1β: interleukin beta; IL-8: interleukin 8; IL-13: interleukin 13; HMGB-1: high-mobility group box protein 1

The immunoprotective function of H 2

Many clinical trials have confirmed the role of H 2 in modulating cancer immunity. A 2018 clinical study involving 55 stage IV colon cancer patients showed that inhalation of H 2 reduced PD-1 expression on CD8 + T cells in the patient’s peripheral blood, reduced CD8 + T cell depletion, and improved prognosis (Akagi and Baba 2019 ). In a clinically advanced small cell lung cancer study, continuous H 2 inhalation for 2 weeks reversed the suppressed intrinsic and adaptive immune systems in patients’ peripheral blood, reduced depleted CD8 + T cells, and restored functional CD4 + , CD8 + T cells, and natural killer cell ratios to normal levels (Chen et al. 2020 ). Although few studies investigate the underlying mechanisms, the ability to selectively clear toxic ROS and protect T cell mitochondria may be the core mechanism of H 2 ’s immune protection function.

After T cell receptor (TCR) activation by antigen-presenting cancer antigens, downstream signal transduction enhances mitochondrial metabolism, and ROS, the apparent byproducts of mitochondrial metabolism, are significant molecules that regulate multiple core pathways involved in T cell metabolic recombination (Franchina et al. 2018 ; Franco et al. 2020 ). However, as previously noted, overgrowing cancer cells can cause elevated ROS in the cancer microenvironment, and mitochondria produce high ROS when T cells are activated, in addition to increased ROS in T cells due to factors such as hypoxia (Scharping et al. 2021 ), which results in tumor-infiltrating lymphocytes (TILs) facing a far higher physiological state of ROS when activated (Franco et al. 2020 ). Sustained high ROS levels disrupt T cell mitochondria, inhibit T cell activation and lead to T cell dysfunction by deflecting T cell metabolic restructuring (Laura 2012 ; Scharping et al. 2016 ), and promote PD-1 expression to induce apoptosis (Najjar et al. 2019 ) (Fig.  4 ). H 2 , on the other hand, combats oxidative stress in various disease conditions and restores redox balance in the body’s environment by regulating the NADH/NADPH pathway (Adzavon et al. 2022 ; Tao et al. 2019 ), thereby safeguarding T cell activation and preventing apoptosis. Moreover, in this condition, compared with routine anti-tumor medicine, the high permeability of H 2 grants it to easily penetrate inside the tumor, even into structures such as the mitochondria of the TILs.

H 2 anti-tumor activity by selectively eliminating ROS in the tumor microenvironment. ROS can cause tumorigenesis by damaging DNA, leading to genetic mutations, and regulating various crucial signaling pathways leading to tumor development and metastasis. ROS in the tumor microenvironment can infiltrate T cells, increasing the oxygen pressure burden of continuously activated T cells. Excessive ROS in T cells can interfere with mitochondrial energy metabolism, damage T cell DNA, and promote PD-1 expression, leading to T cell dysfunction and apoptosis. ROS: reactive oxygen species; EMT: epithelial–mesenchymal transition; Teff: effector T cells; Tex: exhausted T cells. NF-κB: nuclear factor kappa B; MAPK: mitogen-activated protein kinase; mTORC1: mammalian target of rapamycin complex 1

Since the mitochondrial respiratory chain is the primary source of ROS production in cells, high local concentrations of ROS can lead to mutations of mitochondrial DNA and direct disruption of mitochondrial dynamics, ultimately leading to mitochondrial metabolic dysfunction (Deng et al. 2020 ) and apoptosis of T cells(Scharping et al. 2021 ). The study shows that TILs in renal cell carcinoma contain hyperpolarized, fragmented mitochondria producing significant ROS (Siska et al. 2017 ). Akagi et al. found in clinical studies of lung cancer patients (Akagi and Baba 2019 , 2020 ) that inhalation of H 2 enhances the mitochondrial function of CD8 + T cells and decreases PD-1 expression in the patient’s peripheral blood, suggesting that H 2 may act by regulating peroxisome proliferators activate receptor-γ coactivator-1α (PGC-1α). Mo et al. ( 2019 ) suggested that in vitro H 2 can enter mitochondria to neutralize toxic ROS, attenuate mitochondrial oxidative stress damage, protect Na + /Ka + ATP pumps, enhance Bcl-2 expression, inhibit voltage-dependent anion channel 1 (VDAC1) expression and opening, protect mitochondrial membranes, and also inhibit the release of apoptotic factors such as caspase 9.

Application of H 2

Exogenous h 2 administration.

The conventional ways of exogenous administration of H 2 are inhalation, oral HRW, injection of saline containing H 2 , and external use, such as eye drops and HRW baths (Fig. 5 ). Some reviews have compared the rates of H 2 concentration increase in different body organs caused by different H 2 application methods and their therapeutic effects (Li et al. 2019 ; Hirano et al. 2021a ), and we will not present them here individually. However, we cannot simply correlate the role of different H 2 application methods in disease treatment with H 2 concentrations in the circulatory and respiratory systems—for example, the unique role of HRW in regulating intestinal flora and energy metabolism.

Some studies suggest that HRW can regulate intestinal flora and contribute to restoring and maintaining the intestinal flora’s homeostasis (Higashimura et al. 2018 ; Kajiyama et al. 2008 ). In 2018, Japanese scholars (Higashimura et al. 2018 ) found that oral administration of HRW for 4 weeks improves the distribution of flora in the colon, increases SCFA production, and decreases plasma cholesterol concentration. Xiao et al. ( 2018 ) found that HRW could affect intestinal flora by regulating the expression of MyD88, thereby reducing the injury from abdominal radiotherapy and increasing survival and body weight after radiotherapy in mice. HRW has also interacted with diet to enhance and prolong hepatic H 2 accumulation (Kamimura et al. 2011 ), lower blood lipids and glucose, and promote the direct secretion of brain intestinal peptides from intestinal epithelial cells (McCarty 2015 ). In one article (Ito et al. 2012 ), HRW prevented the development of 6-hydroxydopamine-induced Parkinson’s disease in mice, whereas continuous H 2 inhalation and oral lactulose were less effective. Although the article did not explore the underlying mechanisms of this phenomenon, the unique physiological effects of HRW, such as the regulation of intestinal flora, may contribute to it.

Some scientists have designed nanoparticles that can release large amounts of H 2 at cancer sites (Wu et al. 2019 , 2021 ; Sun et al. 2020 ), providing the possibility of precise local production of sustained high concentrations of H 2 to enhance the anti-tumor effect, and the combined application of nanotechnology and H 2 may be an important direction for future precision cancer therapy. For example, Zhang et al. constructed covalently loaded liposomes with semiconductor polymers-Pdots as catalysts (Zhang et al. 2019 ), a “nanoscale H 2 factor” containing reactants, intermediates, and byproducts, which can continuously produce H 2 at the site by laser stimulation and effectively reduce cancer growth in mice. Sun et al. designed a laser-triggered H 2 release nanoparticle to enhance the chemotherapeutic effect of mouse bladder cancer and reduce the toxic response of chemotherapeutic drugs (Sun et al. 2020 ). Wu et al. constructed Au-TiO2@ZnS nanoparticles that can release H 2 triggered by in vitro X-ray under the guidance of in vitro photoacoustic imaging, achieving an excellent therapeutic effect and mild inflammatory response in combination with radiotherapy for in situ liver cancer in mice (Wu et al. 2021 ).

Regulating intestinal flora production of H 2

In addition to the exogenous H 2 supplementation mentioned above, supplementation with high fiber, indigestible starches, and sugars can also increase intestinal H 2 production through intestinal flora, which is the most suitable and economical treatment for daily life (Fig. 5 ).

Lactulose is a disaccharide that cannot be absorbed by the body and can promote large amounts of H 2 production by intestinal flora, thus effectively increasing the concentration of H 2 in the human abdominal cavity and blood. Studies have confirmed that lactulose can relieve inflammation and injury in multiple organs such as the intestine and brain by promoting intestinal H 2 production, such as mitigating ulcerative colitis caused by the carcinogenic substance dextran sodium sulfate (DSS) (Zhai et al. 2013 ; Chen et al. 2013 ). Perlamutrov et al. ( 2016 ) found that lactulose can treat dermatitis by stimulating H 2 and SCFA production. Studies have confirmed that oral administration of lactulose or dietary fiber containing indigestible starch and dietary fiber can regulate intestinal flora (Jiang et al. 2020 ; Trompette et al. 2014 ), balance the intestinal environment, and have therapeutic effects on multi-system diseases such as chronic obstructive pulmonary disease (COPD) and neurological disorders (Vaughan et al. 2019 ; Kong et al. 2021 ). Although some researchers have attributed much of the clinical effects of lactulose and fibrates to specific intestinal flora and SCFAs, H 2 may be an overlooked link in these experiments (Kalantar-Zadeh et al. 2019 ; Desai et al. 2016 ). Similar drugs, fructans, and inulin, also have anti-inflammatory and metabolic-modulating effects by promoting intestinal H 2 production (Nishimura et al. 2013 ).

Perioperative dietary management has profound meaning for the long-term prognosis of cancer patients. To ensure the energy requirements and enhance the immunity of cancer patients, some researchers have proposed the concept of an immunonutrition diet (Adiamah et al. 2021 ; Svetikiene et al. 2021 ; Prieto et al. 2017 ), including glutamine, arginine, sulfur-containing amino acids, and polyunsaturated fatty acids. However, such a high-protein, high-fat diet may cause elevated blood glucose and lipids and metabolic disorders in patients on the one hand, and poor dietary choice may cause adverse emotions in patients on the other hand. As mentioned earlier, oral HRW has a good energy regulation function, which can improve the liver energy metabolism of the body, lower blood lipid glucose, and reduce the side effects of a high-fat diet (Qiu et al. 2020 ). In contrast, some studies show that fiber and indigestible starch diets have anti-inflammatory and anti-tumor effects (Jiang et al. 2020 ; Trompette et al. 2014 ; Desai et al. 2016 ). Therefore, a fiber-rich diet or oral HRW combined with an immunonutritional diet may be a more suitable dietary strategy for cancer patients in the perioperative period.

Various applications of H 2

H 2 in perioperative applications

Clinically, tumors often need surgical treatment, so they inevitably face multiple perioperative stress factors such as trauma, anesthesia, and mental stress. Rapidly elevated oxidative stress can lead to an imbalance of internal environmental homeostasis and immune system suppression in tumor patients while promoting tumor recurrence and metastasis (Hsiao et al. 2021 ; Matzner et al. 2020 ; Seckler et al. 2020 ). H 2 has physiological effects of antioxidant, anti-inflammatory, and immune modulation, which can effectively antagonize these unfavorable factors (Sano et al. 2018 ) (Fig. 6 ).

In addition, H 2 can effectively alleviate ischemia–reperfusion injury in multiple organs (Dong et al. 2018 ; Xie et al. 2020 ; Fu and Zhang 2022 ). For example, in a randomized controlled clinical trial of 26 patients (Ono et al. 2017 ), Ono et al. found that 3% H 2 inhaled twice daily for 1 h significantly improved vital signs, stroke scale scores, physiotherapy index, and 2-week brain MRI in stroke patients compared with conventional treatment.

Postoperative cognitive dysfunction (POCD) is a postoperative complication in patients undergoing clinical procedures and is particularly prevalent in older patients. Currently, the recognized etiology of POCD is neuroinflammation caused by the combined effects of anesthetics and surgery-induced systemic inflammation (Lai et al. 2021 ). H 2 supplementation alleviates symptoms of central nervous system disorders such as Parkinson’s disease and autism by redressing intestinal flora imbalance (Suzuki et al. 2018 ; Kong et al. 2021 ; Doifode et al. 2021 ). Li et al. ( 2010 ) reported that intraperitoneal injection of hydrogen-rich saline effectively alleviated central nervous system inflammation and oxidative stress and reduced cognitive impairment in mice. Therefore, some researchers have stated that H 2 can be used for neuroprotection in perioperative patients (Wang et al. 2020 ) (Fig.  6 ).

The multiple roles of hydrogen in the perioperative period for oncology patients. Hydrogen has been reported to have antioxidant and anti-inflammatory effects and to improve ischemia–reperfusion in the heart, brain, lungs, and other organs, making it possible to alleviate perioperative oxidative stress and ischemia–reperfusion injury in vital organs. Hydrogen also has a neuroprotective function, antagonizing the damage to the central nervous system caused by anesthetics and systemic inflammation. In addition, hydrogen-rich water has energy-regulating and intestinal flora-modulating effects, which are also valuable in the perioperative dietary management of oncology patients

Conclusion and perspectives

The H 2 produced by intestinal flora is a natural antioxidant in the body’s internal environment, which can regulate oxidative stress caused by various reasons in the body’s internal environment and become a natural barrier against carcinogenesis and development. H 2 is also a substrate for the production of SCFAs through the intestinal flora, essential substances for maintaining the stability of the body’s immune system and affecting the gut–brain axis and the gut–lung axis. However, there may be more potential mechanisms for why H 2 has such a wide range of effects. For example, HRW can promote the production of ghrelin (McCarty 2015 ), which is crucial in regulating food intake and energy homeostasis. Therefore, whether H 2 can affect the body’s immune system by regulating the secretion of other flora metabolites or affecting energy metabolism by other gastrointestinal hormones needs further investigation.

Intestinal flora and cancers have long attracted widespread medical attention, and scholars in several countries have actively studied the relationship between genomics and metabolomics of intestinal flora and cancers (Song et al. 2020 ; Fulling et al. 2019 ; Erny and Prinz 2020 ). In those studies, researchers suggest that sulfate-reducing bacteria are related to colorectal cancer (Nguyen et al. 2020 ). More analysis of a large sample of intestinal flora genomics from the perspective of H 2 metabolizing flora and insight into the association between intestinal flora H 2 metabolism and cancer may be able to find new drug targets and guide the subsequent application of H 2 in cancer therapy. For example, some researchers explored the significance of the H 2 metabolism of microbiota through genomic and meta-genomic surveys of the distribution of hydrogenase subtypes (Greening et al. 2016 ; Peters et al. 2015 ).

Studies have shown that H 2 inhalation for about 2 weeks can restore the body’s redox balance and enhance immune cells’ function in the peripheral blood of cancer patients, which indicates that H 2 has a protective effect on the overall immune system of the body. However, in-depth studies on the specific effects of H 2 on TILs in the cancer microenvironment and its potential mechanisms are still lacking. However, according to some studies (Akagi and Baba 2020 ), H 2 can protect the mitochondria of TILs by scavenging ROS, preventing the differentiation of TIL toward the end-stage phenotype, and acting as a qualified adjuvant immunotherapeutic agent. Therefore, its synergistic therapeutic effects with immune checkpoint blockers are yet to be studied.

Furthermore, some studies suggested HRW can regulate the energy metabolism of hepatocytes and adipocytes (Kajiyama et al. 2008 ; Kamimura et al. 2011 ; Acker et al. 2021 ; Iio et al. 2013 ). Although it remains to be investigated whether H 2 can play a role in energy metabolism in cancer cells or immune cells similar to that in hepatocytes and adipocytes, those researches indicated that HRW may exert a more comprehensive potential in anti-tumor immunotherapy by regulating immunometabolism.

There is often cross-talk between gas signaling molecules. For example, H 2 S and NO can regulate each other’s production and enhance each other’s anti-tumor effects (Jing et al. 2021 ). Moreover, it is not difficult to find the intrinsic connection between H 2 and other gas signaling molecules, such as sulfate-reducing bacteria can metabolize H 2 to produce H 2 S, which are in some delicate balance in the intestine. H 2 can regulate CO production through HO-1 (Yu et al. 2019 ), and H 2 can inhibit inducible nitric oxide synthase (iNOS) and enhance the expression of endothelial nitric oxide synthase (eNOS) (Slezak et al. 2021 ). Combining H 2 with other gas signaling molecules may be the development direction of H 2 for cancer treatment, and some studies have suggested this idea in nanotechnology (Jing et al. 2021 ).

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

Apoptosis-inducing factor

Adenosine monophosphate activated protein kinase

Antioxidant response element

Nitric oxide

Chronic obstructive pulmonary disease

Cytotoxic T lymphocyte-associated protein 4

Deoxyribonucleic acid

Dextran sodium sulfate

Fibroblast growth factor

Secretion stimulating receptor for endogenous growth hormone-1a

Glutathione peroxidase

Gas signaling molecules

Hydrogen peroxide

Hydrogen sulfide

Heme oxygenase-1

Hydrogen rich water

Interleukin

Inducible nitric oxide synthase

Kelch-like ECH-associated protein 1

Mammalian target of rapamycin

Nicotinamide adenine dinucleotide

Nicotinamide adenine dinucleotide phosphate

Nuclear transcription factor kappa b

NADPH oxidase

Nuclear factor erythroid-2-related factor 2

Oxidative phosphorylation

Programmed cell death 1

Programmed cell death ligand 1

Peroxisome proliferators activate receptor-γ coactivator -1α

Partial pressure of hydrogen

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This research was supported by the National Key Research and Development Program of China (NO. 2020YFC2008400), the National Natural Science Foundation of China (NO.81873948), the Clinical Research Plan of SHDC (NO. SHDC2020CR1005A). All figures were created with BioRender.com and have publication and licensing rights.

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Miao CH conceived the idea and was responsible for the overall direction. Chen WK wrote the article and was responsible for the overall direction and planning. Zhou WC and Zhang J prepared figures and contributed to the writing of the article.

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Zhou, W., Zhang, J., Chen, W. et al. Prospects of molecular hydrogen in cancer prevention and treatment. J Cancer Res Clin Oncol 150 , 170 (2024). https://doi.org/10.1007/s00432-024-05685-7

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Treatment Research

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Women are more likely than men to experience severe side effects from cancer treatments such as chemotherapy, targeted therapy, and immunotherapy, a new study finds. Researchers hope the findings will increase awareness of the problem and help guide patient care.

Research to improve CAR T-cell therapy is progressing rapidly. Researchers are working to expand its use to treat more types of cancer and better understand and manage its side effects. Learn how CAR T-cell therapy works, which cancers it’s used to treat, and current research efforts.

Experts say studies are needed on how to best transition telehealth from a temporary solution during the pandemic to a permanent part of cancer care that’s accessible to all who need it.

Removing immune cells called naive T cells from donated stem cells before they are transplanted may prevent chronic graft-versus-host disease (GVHD) in people with leukemia, a new study reports. The procedure did not appear to increase the likelihood of patients’ cancer returning.

A specific form of the HLA gene, HLA-A*03, may make immune checkpoint inhibitors less effective for some people with cancer, according to an NCI-led study. If additional studies confirm the finding, it could help guide the use of these commonly used drugs.

The success of mRNA vaccines for COVID-19 could help accelerate research on using mRNA vaccine technology to treat cancer, including the development of personalized cancer vaccines.

Aneuploidy—when cells have too many or too few chromosomes—is common in cancer cells, but scientists didn’t know why. Two new studies suggest that aneuploidy helps the cells survive treatments like chemotherapy and targeted therapies.

New research suggests that fungi in the gut may affect how tumors respond to cancer treatments. In mice, when bacteria were eliminated with antibiotics, fungi filled the void and impaired the immune response after radiation therapy, the study found.

FDA has approved belumosudil (Rezurock) for the treatment of chronic graft-versus-host disease (GVHD). The approval covers the use of belumosudil for people 12 years and older who have already tried at least two other therapies.

In lab studies, the antibiotic novobiocin showed promise as a treatment for cancers that have become resistant to PARP inhibitors. The drug, which inhibits a protein called DNA polymerase theta, will be tested in NCI-supported clinical trials.

A drug called avasopasem manganese, which has been found to protect normal tissues from radiation therapy, can also make cancer cells more vulnerable to radiation treatment, a new study in mice suggests.

While doctors are familiar with the short-term side effects of immune checkpoint inhibitors, less is known about potential long-term side effects. A new study details the chronic side effects of these drugs in people who received them as part of treatment for melanoma.

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A comprehensive analysis of patients with cancer who had exceptional responses to therapy has revealed molecular changes in the patients’ tumors that may explain some of the exceptional responses.

Researchers are developing a new class of cancer drugs called radiopharmaceuticals, which deliver radiation therapy directly and specifically to cancer cells. This Cancer Currents story explores the research on these emerging therapies.

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An experimental drug may help prevent the chemotherapy drug doxorubicin from harming the heart and does so without interfering with doxorubicin’s ability to kill cancer cells, according to a study in mice.

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A novel approach to analyzing tumors may bring precision cancer medicine to more patients. A study showed the approach, which analyzes gene expression using tumor RNA, could accurately predict whether patients had responded to treatment with targeted therapy or immunotherapy.

Bone loss associated with chemotherapy appears to be induced by cells that stop dividing but do not die, a recent study in mice suggests. The researchers tested drugs that could block signals from these senescent cells and reverse bone loss in mice.

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A new NCI-supported study showed that altering cancer cell metabolism by feeding mice a diet very low in the nutrient methionine improved the ability of chemotherapy and radiation therapy to shrink tumors.

An NCI-funded clinical trial is testing the immunotherapy drug nivolumab (Opdivo) in people who have advanced cancer and an autoimmune disease, such as rheumatoid arthritis, lupus, or multiple sclerosis, who are often excluded from such trials.

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A new study provides insight into how cancer immunotherapy works and suggests ways to enhance the treatment’s effectiveness. The NCI-led study, published in Science, examined the effect of high potassium levels on T cells.

Pain is a common and much-feared symptom among people with cancer and long-term survivors. As more people survive cancer for longer periods, there is a renewed interest in developing new, nonaddictive approaches for managing their chronic pain.

An Improved Prostate Cancer Biomarker Test May Help Men Avoid Unnecessary Biopsy

Date Posted Monday, April 29, 2024 , by Alyssa M. Voss, M.P.H.

Researchers funded by NCI have developed and validated a new prostate cancer urinary biomarker test that can help differentiate who should proceed for biopsy after an elevated prostate-specific antigen (PSA) test from those who can wait.

The 18-gene test, called MyProstateScore version 2.0, or MPS2, improves upon the earlier version of MyProstateScore (MPS), the validated two-gene algorithm that uses urine prostate cancer antigen 3 ( PCA3 ) and the TMPRSS2:ERG gene fusion to predict the presence of clinically significant prostate cancer among men with elevated serum PSA. Validation of MPS2 was completed through the NCI Early Detection Research Network (EDRN) , and the results were published in JAMA Oncology .

Prostate cancer is the most commonly diagnosed cancer and the fifth leading cause of cancer death among men in the United States, disproportionately affecting African American men. A widely variable disease, prostate cancer can range from low-grade, slow-growing tumors that will never become life-threatening or require treatment, to high-grade, fast-growing cancers that can quickly spread to other parts of the body.

The most widely used prostate cancer screening methods are a PSA blood test and digital rectal exam (DRE), but these methods are imprecise. Though blood PSA levels will be elevated when cancer is present, PSA can also be high with non-cancerous conditions of the prostate, with low-grade, slow growing cancers, or if someone had a recent prior biopsy. Because of this imprecision, researchers have sought additional biomarker tests to use in conjunction with PSA to better identify which men may have a serious or more aggressive cancer that should be treated. As with any cancer screening approach, the goal is to reduce the number of cancer-related deaths.

“Clinicians need effective tools to reduce the harms of prostate cancer screening. One critical screening question that remains is, among men with an elevated PSA, who should have a biopsy”, said Howard Parnes, M.D., chief of the NCI Division of Cancer Prevention (DCP) Prostate and Urologic Cancer Research Group, who was not involved with the study. “The MPS2 has the potential to reduce unnecessary biopsies and is therefore an important step in the right direction.”

The new MPS2 urine test, developed by researchers at the University of Michigan, screens for 18 genetic markers that are highly associated with clinically significant prostate cancers – cancers that can grow quickly and should be monitored or treated – classified as grade group (GG) 2 and higher. The test is intended as an interim step before undergoing prostate biopsy among people who have an elevated PSA. For the test, men provide a urine sample at a clinic visit after DRE.

“This non-invasive test can serve as an added data point when discussing options with patients,” said senior author Arul Chinnaiyan, M.D., Ph.D., S.P. Hicks Endowed Professor of Pathology and Urology and director of the Michigan Center for Translational Pathology at the University of Michigan. “Approximately 75% of men who undergo biopsy do not have a cancer that needs to be treated. The MPS2 test provides additional information that can help avoid invasive biopsies and the discomfort and potential complications they bring.” A standard biopsy procedure involves systematically extracting 12 samples of prostate tissue from pre-specified areas of the gland.

To develop the MPS2 test, the team began by scanning a set of more than 58,000 potential genetic targets from pooled RNA sequencing data from the University of Michigan and the NCI’s The Cancer Genome Atlas. The panel was refined to a set of 54 candidate genes which, after running verification models, was whittled down to 17 genetic risk markers plus one reference gene, KLK3 . The final MPS2 algorithm combines the 18 markers with other clinically relevant factors, such as age, race, and family history, to provide an overall result. Another version of the test, MPS2+, includes information about prostate volume in its algorithm.

The researchers then validated the assay using urine samples collected from 743 patients enrolled in an EDRN cohort of men who attended one of 11 academic sites for prostate biopsy. The samples went through MPS2 in addition to other clinically available prostate cancer biomarker tests for comparison. The results were then compared to patient biopsy results. They found that the MPS2 outperformed other validated prostate cancer biomarker tests at accurately identifying which patients had cancer detected at biopsy.

Further, the test showed a 95% sensitivity and negative predictive value (NPV) for GG2 cancers and 99% sensitivity and NPV for cancers GG3 and above. “This means that for someone who has a negative result, there is a very high confidence that no cancer is present,” said Chinnaiyan. The analysis estimates approximately 40% of unnecessary biopsies could be avoided using MPS2.  

Putting the test to clinical use

So, what happens next? Chinnaiyan says now that the study results have been published, the assay will be submitted for consideration by the National Comprehensive Cancer Network, a group of 33 U.S. cancer centers that develops resources and guidelines to support high quality, equitable cancer care. He hopes the NCCN will include the MPS2 in their nationally recognized prostate cancer screening and clinical management guidelines, which currently endorses the original MPS and other validated biomarker tests.

But there is no need to wait - the test can be used by any clinician as long as a sample is sent to a CLIA-certified reference laboratory. The MPS2 assay has transferred to LynxDx, a diagnostic testing company Chinnaiyan founded to translate genomic biomarker tests into clinical practice. The company is working to have the assay reimbursed through Medicare and private insurance, but in the meantime, fees may be covered through an early access program. Ultimately the U.S. Food and Drug Administration will need to review and approve MPS2 if the test will be publicly marketed.

Important limitations of the validation study are also going to be addressed in ongoing research. Black men and men of races and ethnicities other than White have disproportionately high rates of prostate cancer mortality. Because the validation cohort included just 4% of its samples from African American men, additional studies are being done in EDRN cohorts that are more racially diverse to ensure the assay’s performance. Additionally, the assay will be validated in a population screened with multiparametric MRI, which provides a more informative three-dimensional image of the prostate and is becoming more frequently used as a second-line assessment after PSA.

The NCI Early Detection Research Network

The Early Detection Research Network (EDRN) is a collaborative program that maintains comprehensive infrastructure and resources critical to the discovery, development and validation of biomarkers for cancer risk and early detection.

Administered through DCP’s Cancer Biomarkers Research Group (CBRG), EDRN connects multidisciplinary teams across the United States to fill gaps that had traditionally plagued the biomarker development process.   Linking key players in the biomarker discovery, assay development, and validation areas allows seamless transition of candidate markers through the pipeline. The infrastructure also provides shared resources such as data and biologic samples, consultation and advisory services, and funding to ensure promising cancer biomarkers meet the highest standards for accuracy and quality through the network’s rigorous standardized testing protocols.

“The development of the MPS2 test provides an important, progressive improvement in current methods for the early detection of prostate cancer, said Sudir Srivastava, Ph.D., M.P.H, EDRN program director and chief of CBRG. “It takes a village of various expert teams to develop and validate an accurate cancer biomarker, and we consider this another EDRN success.”

To learn more about EDRN, visit https://prevention.cancer.gov/major-programs/early-detection-research-network-edrn .

Reference: JJ Tosoian, Y Zhang, L Xiao, et al. Development and validation of an 18-gene urine test for high-grade prostate cancer. JAMA Oncology . 2024 doi:10.1001/jamaoncol.2024.0455

If you would like to reproduce some or all of this content, see Reuse of NCI Information for guidance about copyright and permissions. Please credit the National Cancer Institute as the source and link directly to the blog post using the original title, for example: " An Improved Prostate Cancer Biomarker Test May Help Men Avoid Unnecessary Biopsy was originally published by the National Cancer Institute." For questions, contact us at [email protected] .

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Cancer prevention articles within Nature Reviews Clinical Oncology

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News & Views | 24 February 2015

New standard of care—HPV testing for cervical cancer screening

High-risk human papillomavirus (hrHPV) types cause cervical cancer. Hence, a negative hrHPV test provides excellent reassurance against cervical precancer and cancer, superior to a negative cervical smear (Papanicolaou or Pap) test. Screening first for hrHPV might improve the accuracy and positive predictive value of secondary Pap testing in hrHPV-positive women, and thus guide decisions on what care is needed.

• Philip E. Castle

Review Article | 27 January 2015

Current management of lesions associated with an increased risk of breast cancer

A number of breast lesions that are associated with an increased risk of breast cancer and/or represent true precursors of breast tumours are increasingly detected in population screening programmes. At present, the clinicopathological and molecular characteristics that defined the risk of breast cancer in women with these lesions are unknown; nevertheless, management strategies ranging from active surveillance to surgery with adjuvant radiotherapy and endocrine therapy can be planned based on the risk of breast cancer at the population level. Herein, the contemporary approaches to the diagnosis and management of high-risk breast lesions are comprehensively reviewed.

• Monica Morrow
• , Stuart J. Schnitt
•  &  Larry Norton

Research Highlight | 13 January 2015

Tamoxifen—offering a long-term prevention option

• Alessia Errico

News & Views | 18 February 2014

Targeted therapy—anastrozole prevents breast cancer

The recent IBIS-II clinical trial results demonstrate anastrozole reduces breast cancer incidence by 53% in postmenopausal women. While this is a major advance in prevention research, its impact on clinical practice will ultimately depend upon subject perception of risk, adverse effects and benefits of anastrozole versus other available cancer preventive therapies.

• Powel Brown

Review Article | 26 November 2013

Future directions in the prevention of prostate cancer

Chemoprevention has been increasingly explored to mitigate the global burden of prostate cancer and the overtreatment of indolent disease that has arisen in the prostate-specific antigen screening era. In this Review, the authors summarize the major findings of chemoprevention trials and discuss the future opportunities in this arena.

• Ian M. Thompson Jr
• , April B. Cabang
•  &  Michael J. Wargovich

Review Article | 08 October 2013

Suitable trial designs and cohorts for preventive breast cancer agents

Establishing breast cancer chemoprevention in standard clinical practice requires advances in many different fields, including biomarker research, the development of more powerful tools to predict and communicate the risks and benefits of treatments and establishing innovative trial designs. In this Review, the authors examine the efforts in breast cancer chemoprevention and explain why the field is progressing slowly than hoped.

• Kathrin Strasser-Weippl
•  &  Paul E. Goss

Review Article | 01 October 2013

Beyond aspirin—cancer prevention with statins, metformin and bisphosphonates

Medications commonly used by large populations to treat non-cancerous medical situations are attractive candidates for cancer prevention. This Review discusses three pharmacological agents with chemopreventive potential: statins, metformin and bisphosphonates. The authors outline the pharmacological mechanisms of action of these agents, the supporting clinical evidence for their efficacy and safety in large populations, and discuss how these agents should be used in the ongoing aim of preventing cancer.

• Naomi Gronich
•  &  Gad Rennert

Research Highlight | 03 September 2013

Reduction in the risk of prostate cancer with finasteride

• Vanessa Marchesi

Review Article | 26 March 2013

Aetiology, genetics and prevention of secondary neoplasms in adult cancer survivors

The occurrence of second malignant neoplasms in survivors of cancer is one of the most serious complications of cancer and its treatment. Second and higher-order malignancies now comprise about 18% of all incident cancers in the USA, superseding first primary cancers of the breast, lung, and prostate. This Review article discusses the wide-range of factors that influence the occurrence of second malignant neoplasms and a review of modifiable behavioural and lifestyle factors.

• Lois B. Travis
• , Wendy Demark Wahnefried
•  &  Andrea K. Ng

News & Views | 09 October 2012

Aspirin and the risk of prostate cancer mortality

The observational registry CaPSURE study reported that men with prostate cancer who were taking aspirin were less likely to die of prostate cancer than nonusers. This favourable effect seems to be stronger than that observed in a pooled analysis of randomized clinical trials of aspirin, and in other observational studies.

• Carlo La Vecchia
•  &  Cristina Bosetti

News & Views | 07 August 2012

Upholding the Affordable Care Act—implications for oncology

The Affordable Care Act—the Obama administration's signature legislation designed to insure over 30 million currently uninsured Americans—was recently declared constitutional by the US Supreme Court. Although not perfect, the law contains provisions that will benefit patients with cancer, those at risk of cancer and those in remission.

• Sandra Swain
•  &  Clifford Hudis

Review Article | 03 April 2012

The role of aspirin in cancer prevention

The authors of this Review discuss the mechanism of action of aspirin, current evidence concerning the main health outcomes affected by aspirin use, and the hypothesis that inhibition of platelet activation may mediate both the cardioprotective and cancer-preventive effects of low-dose aspirin.

• Michael J. Thun
• , Eric J. Jacobs
•  &  Carlo Patrono

News & Views | 27 March 2012

Aromatase inhibitors—bone health assessment is crucial

A safety substudy of the MAP.3 trial included 242 women who had completed 2-year follow up (124 given exemestane, 118 given placebo). Exemestane resulted in a significantly higher decrease of bone structural parameters and bone mineral density. Patients receiving exemestane for primary breast cancer prevention should be monitored and treated accordingly.

• Peyman Hadji

Research Highlight | 15 November 2011

Pain killer—cancer preventer

• Rebecca Kirk

Research Highlight | 05 July 2011

MAPping out breast cancer chemoprevention

• Lisa Hutchinson

Correspondence | 31 May 2011

P5 medicine: a plus for a personalized approach to oncology

• Alessandra Gorini
•  &  Gabriella Pravettoni

Opinion | 02 March 2011

Predictive, personalized, preventive, participatory (P4) cancer medicine

The authors takes a systems-biology approach to the problems of personalized cancer medicine. They describe the challenges of moving to a discipline that is predictive, personalized, preventive and participatory and explore methods for overcoming these obstacles.

•  &  Stephen H. Friend

Research Highlight | 31 January 2011

A TRAIL of destruction

• Lisa Richards

News & Views | 04 January 2011

Will an aspirin a day keep the colorectal cancer away?

A long-term follow-up study that assessed the effect of daily aspirin on colorectal cancer incidence concluded that it significantly reduced the risk of colon cancer, but not rectal cancer. Detailed analysis of the findings indicate that it is too soon to recommend daily aspirin for cancer prevention in healthy individuals.

• Marianne Berg
•  &  Kjetil Søreide

Research Highlight | 01 September 2010

Oral bisphosphonate use may protect women from breast cancer

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Cancer vaccines could be game changing, but they’re not a one-shot solution to beating cancer

26 April 2024

The science that helped bring the COVID-19 pandemic under control is continuing to show promise in treating other diseases.   

I recently returned from a large conference of cancer experts in the US where there were several presentations on promising early trials of cancer vaccines. Things are really moving in the right direction to bring this type of treatment to more patients sooner.  

Today’s announcement about Moderna and MSD’s melanoma cancer vaccine moving to Phase 3 clinical trials means the vaccine will now be tested in a larger number of patients with melanoma post-surgery, to ensure it is an effective treatment for this type of cancer.  

If the trial is successful, the same technology could be potentially used to target other cancers in combination with existing treatments such as chemotherapy, radiotherapy and immunotherapy.  

It’s not just Moderna’s COVID-19 vaccine technology being repurposed: Cancer Research UK and the CRIS Cancer Foundation recently announced up to £1.7million funding to investigate whether Oxford-AstraZeneca’s COVID-19 vaccine platform can be used to make LungVax, the world’s first vaccine to prevent lung cancer.  

We also shouldn’t forget that the HPV vaccine has reduced cases of cervical cancer by nearly 90%  in women in their 20s who received the vaccine at age 12 to 13. It’s possible that we could eliminate this cancer type as a public health problem.  

As there are over 200 types of cancer, vaccines are unlikely to be a solution to beating all cancer types. We desperately need a systemic approach to addressing the complex challenges associated with cancer.   

Research must be sufficiently funded to make more breakthroughs possible. We face a R&D funding gap of more than £1billion by the end of the next decade in cancer research. We want to work with all major political parties, industry and academia to ensure we can plug this gap and ensure the innovations of tomorrow reach patients.  

We need long-term strategies for cancer care to help diagnose more cases earlier, reduce inequalities in accessing treatment, and reduce waiting times. We also need to make sure that groundbreaking therapies, should they become available, are accessible to all.  

Cancer vaccines progressing through clinical trials are exciting news. These breakthroughs should give us much cause to be optimistic, but we can’t lose sight of the complex challenges ahead, tackling them head on will benefit all of us in the long run. 

Iain Foulkes

About the author

Iain Foulkes is Executive Director of Research and Innovation at Cancer Research UK  .

This article was originally published in iNews  

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Facing Cancer Head-On

This year, an estimated 65,000 people in the United States will be diagnosed with head and neck cancers. This group of diseases includes cancers of the larynx (voice box), throat, lips, oral cavity, nose, and salivary glands. While prevention measures such as tobacco control and smoking cessation have reduced head and neck cancers overall, oral cancer associated with human papillomavirus (HPV) infection has steadily increased in recent years. Because head and neck cancers often go undetected until they’re quite advanced and are difficult to treat, the survival rate remains around 40-50%, and cancer is likely to recur after treatment.

Patients often experience diminished quality of life. “Many patients with head and neck cancer experience pain, either from the tumor or from treatments like surgery and radiation,” said oncologist Barbara Burtness, M.D., of Yale University. “Even for patients who have been cured, the treatments can result in difficulty swallowing, depriving people of the pleasure of eating and social connection from dining together. Some patients also report chronic pain, speech impairment, or hearing loss.”

Did You Know?

April is Oral Cancer Awareness Month. NIDCR offers resources for the general public to raise awareness of oral cancer:

• For easy-to-read information on oral cancer and other dental, oral, and craniofacial conditions, visit our Health Info page . This information is also available in Spanish .
• Watch a video where NIDCR clinicians show you what to expect during an oral cancer exam. An exam allows health care providers to detect early signs of cancer in the mouth.

To improve patient outcomes, NIDCR-supported researchers have been tackling head and neck cancers from multiple angles. In addition to traditional chemotherapy and radiation therapy, many scientists are tapping into immunotherapy, leveraging the immune system with cancer vaccines and tumor-killing therapies. Others are investigating the crosstalk between cancer cells and nerves that promotes disease progression. In the clinic, scientists are developing devices and computer algorithms to help dental professionals map suspicious lesions in the mouth for biopsies and early detection. Researchers are also studying HPV vaccine implementation, hesitancy, and uptake. In many cases, these research efforts have been supported through partnerships with the National Cancer Institute (NCI), including the recently launched Advancing Head and Neck Cancer Early Detection Research (AHEAD) initiative.

“While we have gained a wealth of knowledge about the biology of head and neck cancers over the past decades, the statistics around their morbidity and mortality show there is much more work to be done,” said NIDCR Deputy Director Jennifer Webster-Cyriaque, D.D.S., Ph.D. “These discoveries must be translated into practical solutions — prevention strategies, early detection methods, and novel therapies — for the benefit of all patients.”

The Network that Feeds Cancer

Clinicians have had limited success in tackling cancer partly because the disease has a strong support system. The networks of connective tissue, blood vessels, and nerves that surround tumor cells mutually support each other in a way that fuels cancer development and progression.

A recent study at MD Anderson Cancer Center showed that mice lacking p53, a protein that normally restrains cancer growth, had denser nerve networks around oral tumors than mice with p53. First author Moran Amit, M.D., Ph.D., senior investigator Jeffrey Myers, M.D., Ph.D., and their colleagues found that the loss of p53 allowed tumor cells to reprogram healthy nerves into cancer-promoting ones. They confirmed the finding in oral cancer patients and revealed that p53 status was associated with nerve density and poor clinical outcomes. The research suggests that interrupting crosstalk between tumors and nerves may lead to potential therapies.

Nisha D’Silva, B.D.S., M.S.D., Ph.D., and her team at the University of Michigan devised a metric to further articulate the tumor-nerve relationship by measuring nerve density around tumors. The group found that higher nerve density enhanced tumor growth in animals and was associated with lower oral cancer survival rates in humans. The method could one day help clinicians identify aggressive tumors and inform the best course of treatment.

Tapping into the Body’s Defense System

Cancers are cunning. To avoid attacks from the immune system, cancer cells can display proteins on their surfaces that disguise them as healthy cells. Clinicians have been prescribing a type of immunotherapy called immune checkpoint inhibitors, which counteract these protein disguises to enable the immune system to recognize and kill tumor cells. This class of drugs has shown promise for treating a small percentage head and neck cancers, as well as other types of cancers, such as lung and skin cancers.

Unfortunately, many cases of head and neck cancer are resistant to these therapies — only 15-20% of patients respond to them. Dr. Burtness, the Yale oncologist, wants to fix that. Her team is funded by NIDCR and NCI through the Specialized Programs of Research Excellence (SPORE), an NCI initiative to rapidly move basic science findings into clinical interventions. The Yale scientists plan to identify cancer-driving biological pathways unique to head and neck cancer to develop more effective therapies. They're exploring treatments that trigger deadly DNA changes in cancer cells in combination with immune checkpoint inhibitors, and they aim to verify their findings in clinical trials.

At the Dana-Farber Brigham Cancer Center, head and neck cancer surgeon Ravindra Uppaluri, M.D., Ph.D., is investigating another strategy: cancer vaccines. Like traditional vaccines that train the immune system to recognize and kill viruses, cancer vaccines teach the body’s immune cells to recognize cancer-specific proteins on tumor cell surfaces. Using a mouse model of head and neck cancer, Dr. Uppaluri’s group asked why certain vaccines generate strong responses while others do not.

They tested two different vaccines that act against tumor cell proteins called mICAM1 and p15E. Both vaccines triggered a response from cancer-killing immune assassins called CD8+ T cells. However, the mICAM1 vaccine additionally elicited a reaction from CD4+ T cells, which help enhance immune attacks. Compared to mice given the p15E vaccine, mICAM1-vaccinated mice had slower tumor growth and survived longer, highlighting a role for CD4+ T cells in boosting immune responses to cancer. The findings may help researchers understand how to develop better head and neck cancer vaccines.

Dr. Uppaluri also received a Cancer Moonshot grant co-funded by NCI and NIDCR through the Immuno-Oncology Translational Network. Cancer Moonshot is a White House initiative led by NCI to accelerate cancer research, improve patient care, and end cancer as we know it. Network scientists aim to improve immunotherapy outcomes and prevent cancers before they occur. Dr. Uppaluri is working to understand the biology of immunotherapy resistance in head and neck cancers.

In a clinical trial, Dr. Uppaluri and his team treated patients with two doses of a type of immune checkpoint inhibitor called anti-programmed cell death protein 1 before surgically removing head and neck tumors. They found that 45% of the patients had some response to this treatment, including signs of cancer cell death in the collected tumors under the microscope. They also discovered that people who responded well to the treatment had higher levels of certain immune cells compared to those whose tumors were resistant. The findings suggest that the activation of these immune cells is crucial for successful therapy and could help clinicians identify patients who may respond better to these therapies.

Nipping Head and Neck Cancer in the Bud

Another facet of NIDCR’s head and neck cancer research focuses on finding ways to lower the risk of cancer developing in the first place. Scientists have identified certain risk factors for head and neck cancers, including HPV infection, heavy alcohol use, and cigarette smoking. Studies have shown that reduced cigarette smoking in recent years is linked to declining rates of tobacco-associated head and neck cancer. But growing evidence also suggests that e-cigarette use, or vaping, may be just as harmful as cigarette smoking.

A team led by Ahmad Besaratinia, Ph.D., M.P.H., at the University of Southern California found that vapers and smokers had similar levels of DNA damage in oral cavity-lining cells — more than twice the amount found in non-users. DNA damage is early changes in cells that can contribute to cancer and other chronic diseases. In the study, the more a person smoked or vaped, the more DNA damage there was, suggesting that vaping may be just as likely as cigarette smoking to cause changes potentially relevant to cancer in the mouth.

Catching cancer early and intervening promptly can change the course of disease progression. When head and neck cancer is detected early, patients have a five-year survival rate of up to 80%, compared to about 20% for late-stage disease. The gold standard for screening is to biopsy suspicious tissues, a technique that relies heavily on the experience of the clinician. Knowing when and where to look can be challenging, even for the most seasoned providers.

Scientists at Rice University and MD Anderson Cancer Center, led by Rebecca Richards-Kortum, Ph.D., designed a portable imaging system to help clinicians spot suspicious oral lesions. This system can create a cancer risk and biopsy guidance map based on photos, fluorescence imaging, and microscopy images of the patient’s oral tissues. These maps are then physically projected onto the patient’s mouth, highlighting the most suspicious-looking areas where clinicians should consider taking biopsies. This real-time visualization process can be completed by clinicians in just minutes. The research team is working to further optimize the system to enhance its diagnostic potential.

Most recently, NIDCR partnered with NCI to launch the AHEAD program , which aims to promote biomarker development to help clinicians detect cancer early, prevent cancer growth, and monitor treatment responses to curb recurrence. Biomarkers are molecules found in blood, body fluids including saliva, or tissues that predict or signal the presence of cancer. In 2023, NIDCR, together with NCI, awarded seven grants totaling $4.4 million for up to five years of support. With access to NIDCR and NCI resources and infrastructure, such as NCI’s Early Detection Network, researchers are mapping the immune, genetic, and protein changes that drive suspicious oral lesions into cancers.

“NIDCR-supported research has patients’ best interests in mind,” said Zhong Chen, M.D., Ph.D., director of NIDCR’s Oral and Salivary Cancer Biology Program. “We are in a very exciting era with fascinating technological advances in biology, medicine, and computation that will move us collaboratively toward a future where head and neck cancer can be better prevented, diagnosed earlier, and treated more effectively.”

Related Links:

• The Many Long, Intrusive Arms of Cancer Cell Invasion
• Exploring AI for Cancer Diagnosis
• A Cancerous Conversation Fuels Oral Tumors
• How to Build a Cancer

References:

• Amit M, Takahashi H, Dragomir MP, Lindemann A, Gleber-Netto FO, Pickering CR, et al. Loss of p53 drives neuron reprogramming in head and neck cancer . Nature. 2020 Feb;578(7795):449-454. doi: 10.1038/s41586-020-1996-3. Epub 2020 Feb 12.
• Perez-Pacheco C, Schmitd LB, Furgal A, Bellile EL, Liu M, Fattah A, et al. Increased Nerve Density Adversely Affects Outcome in Oral Cancer . Clin Cancer Res. 2023 Jul 5;29(13):2501-2512. doi: 10.1158/1078-0432.CCR-22-3496.
• Shibata H, Xu N, Saito S, Zhou L, Ozgenc I, Webb J, et al. Integrating CD4+ T cell help for therapeutic cancer vaccination in a preclinical head and neck cancer model . Oncoimmunology. 2021 Aug 10;10(1):1958589. doi: 10.1080/2162402X.2021.1958589.
• Oliveira G, Egloff AM, Afeyan AB, Wolff JO, Zeng Z, Chernock RD, et al. Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti-PD-1 in head and neck cancer . Sci Immunol. 2023 Sep 8;8(87):eadf4968. doi: 10.1126/sciimmunol.adf4968.
• Tommasi S, Blumenfeld H, Besaratinia A. Vaping Dose, Device Type, and E-Liquid Flavor are Determinants of DNA Damage in Electronic Cigarette Users . Nicotine Tob Res. 2023 May 22;25(6):1145-1154. doi: 10.1093/ntr/ntad003.
• Coole JB, Brenes D, Mitbander R, Vohra I, Hou H, Kortum A, et al.  Multimodal optical imaging with real-time projection of cancer risk and biopsy guidance maps for early oral cancer diagnosis and treatment . J Biomed Opt. 2023 Jan;28(1):016002. doi: 10.1117/1.JBO.28.1.016002. Epub 2023 Jan 13.

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Development in cancer treatment focuses on re-educating cells to combat resistance

by Charles University

In a development in cancer research, scientists are exploring new therapeutic strategies that move beyond traditional cytotoxic treatments, which have historically targeted uncontrolled cell proliferation.

"These conventional methods often result in the survival of resistant cancer cells, ultimately leading to tumor progression and treatment failures," said correspondent author of the study, professor Jan Brábek from the Faculty of Science, Charles University. In response, researchers are now focusing on alternative approaches aimed at modifying cancer cell behavior to prevent the development of resistance.

The work is published in the journal Trends in Molecular Medicine .

The new strategies, as detailed in recent scientific findings, include:

• Controlling Cell Dormancy—By regulating the dormancy of cancer cells, researchers aim to prevent them from proliferating uncontrollably.
• Transdifferentiation Therapy—This approach encourages cancer cells to change into less harmful types, potentially reducing their malignancy.
• Normalizing the Cancer Microenvironment—By correcting the environment around cancer cells, this strategy aims to inhibit their growth and invasiveness.
• Migrastatic Therapy—Focusing on preventing the migration of cancer cells , this therapy aims to stop cancer from spreading to other parts of the body.

"Unlike traditional methods, these innovative approaches do not provide resistant cells with a direct proliferative advantage. This key difference means that even if some cells adapt, they do not lead to aggressive or resistant tumors," said Brábek.

Thus, these strategies hold substantial promise in effectively delaying or even preventing the development of therapy-resistant tumors, offering new hope to patients worldwide.

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National Cancer Institute - Cancer.gov

Study sheds light on diversity of study participants at CCR

Diversity in clinical trials is critical for understanding how well a treatment may work in different populations. A new study done by CCR researchers describes representation based on sex, age and ethnicity in clinical trials done at CCR. Image credit: iStock

A recent study analyzing the demographics of clinical trial participants at CCR describes the representation of various population groups in cancer research. The results, published February 19 in the  Journal of the National Cancer Institute , suggest that older adults, women, Asians, Hawaiians, Pacific Islanders, American Indians, Alaska Natives, and Hispanics are underrepresented in clinical trials done by CCR, while Blacks or African Americans have higher representation.

People can respond differently to treatments depending on their biology, including ancestry and biological sex. For these reasons, it is important for clinical trials investigating new therapies to include diverse populations.

“By including every population in a clinical trial, you can have higher confidence to say who will benefit from a certain therapy,” explains  Charalampos “Harris” Floudas, M.D., DMSc, M.S. , Assistant Research Physician in the  Center for Immuno-Oncology .

Floudas and his team sought to better understand the diversity of clinical trials conducted by CCR. They analyzed demographic data capturing the sex, age, race and ethnicity of 38,531 people who enrolled in clinical trials for cancer treatment at CCR between 2005 and 2020, in comparison to similar demographic data of the general population that goes on to develop a given type of cancer (called the incidence rate).

In the past, Black and African American populations have often been under-represented in research. However, the results of this study show that Black and African American populations are currently represented well in CCR trials, likely because this population is very prevalent in the Maryland and Washington D.C. area, where the National Cancer Institute is located.

Older adults, women, Asians, Hawaiians or Pacific Islanders, American Indians or Alaska Natives, and Hispanics or Latinos are underrepresented in these clinical trials, to varying degrees. For example, women develop 49.5% of all cancers included in this study, but they represent 41.7% of participants in CCR clinical trials. Whereas Hispanic cancer patients make up 13% of the overall cancer cases included in this study, they represent only 7.1% of participants in CCR clinical trials.

The researchers speculate that some of these under-represented groups, such as older adults with mobility issues and Native Americans living in rural and remote areas, may experience difficulties in traveling to the CCR clinics to receive treatment, underscoring the importance of programs that provide funding and support for treatment-related travel.

Of note, the researchers found that the overall proportion of older adults, African Americans, Asian/Pacific Islanders, and Hispanic participants in these trials increased over the 15 years of this study, indicating positive participation trends for these groups. However, an increase in representation of women did not occur over this same time period, indicating that more targeted strategies to support their participation in studies are especially needed.

Floudas notes that this study is only a first look at CCR’s trial participation, however, and it is a positive initial step toward new strategies for increasing diversity in trials. His team plans to conduct a follow-up study for older adults across race and ethnicity, which will inform future recruitment strategies for clinical trials.

This research was made possible with the collaboration amongst CCR researchers Harris Floudas, M.D., DMSc, M.S., James Gulley, M.D., Ph.D., Fatima Karzai, M.D., and Nirmal Choradia, M.D. In the Q&A that follows, they each elaborate on the background of this study and possible future directions.

What was the inspiration behind the need to conduct the study?

JG : We have all realized that access to clinical trials is not equitable and I believe we can increase diversity in clinical trials and gain insights about the applicability of findings to diverse patient populations. However, to do this, we have to first measure where we are with our current cancer patient populations.

FK : This study is a foundation for determining what we are doing well but also what we can do better in the recruitment and retention of under-represented minorities in clinical trials. The CCR community needs to tackle under-representation in clinical trial accrual as a collective, and this type of study helps to start defining that path.

What is the importance of studying and understanding the demographics in past clinical trials?

HF : Detailed analysis of the demographics is necessary to establish if there is a problem (underrepresentation) with a specific clinical trial, and if so, to understand potential reasons for this problem. Data are required to validate our hypotheses and allow us to consider ways to improve.

What are the future directions for this research? How do you hope these findings will be used?

FK : We will use this study as a starting point and go on to determine ways in which to improve diversity in clinical trials at CCR. First, data capture for sex, race, and ethnicity needs to be improved for all clinical trials (including self-reporting). Next, understanding our catchment areas and how to expand upon them is important and stems from this research. We can identify what barriers we can address to increase opportunities for clinical trial exposure. This is multi-factorial, involving reaching out to the communities affected, as well as expanding the ways in which patients are exposed to learning about clinical research.

NC:  We would ideally like to identify places that have good relationships with specific oncology groups at CCR and provide this information to them to increase outreach. I also think spreading knowledge about what the NCI has to offer and the research we conduct would help build a more diverse patient population. It would be valuable to have more discussions with patients and advocacy groups as to areas of outreach to broaden our reach.

What do you think are the most effective methods for increasing diversity in clinical trials?

HF: Consistent, targeted outreach to the recognized underrepresented populations will be necessary, proportional to the magnitude of underrepresentation. Studying the factors limiting accessibility for patients and ways to simplify the referral process will be key to facilitating potential participants and their providers.

FK: This requires collaboration, determination, and multifaceted efforts. Our recommendations include collecting data about patient experiences to identify strengths and opportunities for improvement, strengthening the delivery of culturally sensitive communications and patient-centered care, implementing metrics to assess accrual and diversity in accrual to clinical trials, and institutional partnerships to increase awareness of CCR clinical trials. It is imperative to make a meaningful difference for our patients by being firmly committed to increasing diversity, equity and inclusion in our clinical trials. This should be at the forefront of our scientific endeavors as it will improve scientific rigor and the quality of healthcare we deliver.

The new  Office of Healthcare Delivery and Equity Research at CCR also leads institutional efforts in multiple ways. Associate Director Brenda Adjei, Ed.D., M.P.H., provides a glimpse of other CCR-wide efforts to increase diversity in clinical trial enrollment.

The analyses conducted by Choradia et al., 2024, provide an important first step toward identifying opportunities to enhance equitable representation in NCI’s clinical research. This is not only important in terms of enriching cancer research – it is a critical aspect of fulfilling the NCI mission to reduce the cancer burden for all. Our new office builds on strong leadership support and commitment to this goal, and the foundational efforts of CCR’s Clinical Trials Diversity and Inclusion Committee, which outlined recommendations to strengthen healthcare delivery and equity in CCR.

To overcome barriers to clinical trial participation among populations underrepresented in clinical research, our new office has prioritized improving data collection, building and enhancing clinical and community engagement efforts, and implementing multilevel and evidence-based initiatives in collaboration with our CCR clinical teams. The demographic data reported in this paper highlight the need to understand who our patients are and how we can best address their cancer care needs. This approach (called “catchment area analysis”) will help us to strengthen our metrics and data systems, understand what outreach has been effective, and what innovative models and engagement strategies on which we should focus. This data will also inform targeted and tailored efforts to increase awareness of CCR’s clinical research among clinical and community partners, reduce barriers to clinical trial participation among diverse population groups, and enhance efforts to provide culturally and linguistically appropriate patient-centered care at CCR.

Similar to the national cancer care community, CCR leadership has prioritized the implementation of initiatives to improve access, outreach, engagement, and diversity in CCR clinical trials. We have a lot to do and are excited about our planned efforts to engage with our local and national clinical and community partners in providing access to NCI’s clinical trials.

The team would also like to thank the NIH Biomedical Translational Research Information System (BTRIS) team for providing the data that made this study possible.

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