AACR CANCER PROGRESS REPORT 2023 SPOTLIGHT ON Immunotherapy AACR.org CancerProgressReport.org #CancerProgressReport
AACR CANCER PROGRESS REPORT 2023 AACR.org CancerProgressReport.org #CancerProgressReport PLEASE CITE THIS REPORT AS: American Association for Cancer Research. AACR Cancer Progress Report [Year]. Accessed on: [Month],[Year]. Available at: cancerprogressreport.org ISBN: 979-8-9857852-4-1 Cover design by John B. McCullough
Table of Contents A Message from AACR..................................................1 Executive Summary......................................................3 A Snapshot of a Year in Progress.............................10 Cancer in 2023..............................................................12 Research: Driving Progress Against Cancer.......12 Cancer: An Ongoing Public Health Challenge.....14 Inequities in the Burden of Cancer in the United States...............................................................15 Variable Progress Against Different Types of Cancer and Stages of Diagnosis..................................20 The Growing Population Burden of Cancer...................20 The Global Burden of Cancer.............................................21 Funding Cancer Research: A Vital Investment...22 Understanding the Path to Cancer Development..................................................24 Cancer Development: Generating Knowledge....24 Basic Research: Vital for Making Progress Against Cancer....................................................27 Cancer Development: Interpreting Knowledge...29 Changes That Contribute to Cancer Initiation..............29 Genetic Alterations...............................................................29 RNA Variations........................................................................31 Protein Modifications...........................................................32 Epigenetic Changes.............................................................32 Systems That Enable Cancer Progression......................32 The Blood System.................................................................32 The Lymphatic System........................................................33 The Immune System.............................................................34 Processes That Promote Cancer Growth and Metastasis.......................................................................34 Tumor Heterogeneity...........................................................34 Epithelial-to-mesenchymal Transition...........................35 Tumor Microenvironment...................................................35 Cancer Development: Integrating Knowledge.....35 Reducing the Risk of Cancer Development...........38 Eliminate Tobacco Use............................................38 Maintain a Healthy Weight, Eat a Healthy Diet, and Stay Active.................................41 Reduce Risk of Diabetes.........................................44 Limit Alcohol Consumption...................................46 Protect Skin from UV Exposure.............................47 Prevent and Eliminate Infection from Cancer-causing Pathogens.....................................48 Limit Exposure to Environmental Risk Factors...51 Be Cognizant of Hormonal Factors......................52 Pregnancy and Breastfeeding...........................................52 Hormone Replacement Therapy.......................................53 Screening for Early Detection..................................54 Importance of Cancer Screening........................54 Guidelines for Cancer Screening.........................58 Eligibility for Cancer Screening..........................59 Those at an Average Risk of Being Diagnosed with Cancer.......................................................60 Those at a Higher-Than-Average Risk of Being Diagnosed with Cancer............................................61 Suboptimal Uptake of Cancer Screening............61 Progress Toward Increasing Adherence to Cancer Screening Guidelines........................................64 New Frontiers in Cancer Screening....................65 Realizing the Potential of Artificial Intelligence for Early Detection of Cancers..........................................65 Moving Toward Minimally Invasive Cancer Screening....65 Advancing the Frontiers of Cancer Science and Medicine................................................................68 Clinical Research ..................................................68 Progress Across the Clinical Cancer Care Continuum.........................................71 Advances in Cancer Treatment with Surgery................74 Improving Quality of Life After a Cancer Surgery.....74 Visualizing Lung Cancers More Precisely During Surgery ......................................................................78 Improvements in Radiation-based Approaches to Cancer Care.......................................................................79 Imaging Prostate Cancer More Clearly.........................82 Advances in Treatment with Cytotoxic Chemotherapy....................................................82 Advances in Treatment with Molecularly Targeted Therapy..................................................................83 Expanding Treatment Options for Patients with Lung Cancer..................................................................83 Targeting Cancers Based on a Common Genetic Feature, Not Tissue of Origin...........................85 Delivering a Cytotoxic Drug Precisely to Ovarian Cancer Cells......................................................86 Improving Outcomes for Patients with Metastatic Breast Cancer.........................................86 Personalizing Treatment for Patients with a Rare Solid Tumor ....................................................87 Combining Molecularly Targeted Therapeutics to Block Tumor Growth.......................................................90 AACR Cancer Progress Report 2023 ii
Adding Precision to the Treatment of Blood Cancers....................................................................91 Blocking Progression of Metastatic Prostate Cancers...................................................................98 SPOTLIGHT Immunotherapy: Pushing the Frontier of Cancer Medicine.....................................................99 Cancer Immunotherapy and How It Works........99 Releasing the Brakes on the Immune System..............101 Boosting the Cancer-killing Power of Immune Cells...109 Adoptive Cell Therapy.......................................................109 Enhancing Immune Cell Function...................................117 Directing the Immune System to Cancer Cells...........120 Current Challenges in Cancer Immunotherapy.......................................125 Knowledge Gaps in Predicting Response to Immunotherapy...............................................................125 Adverse Effects of Immunotherapy................................125 Disparities in Access to Immunotherapy.......................126 On the Horizon for Immunotherapy..................128 A New Era of mRNA-based Cancer Vaccines..............128 A New Generation of Immune Checkpoint Inhibitors.........................................................128 A New Wave of Adoptive Cell Therapeutics................129 A New Age of Therapeutic Combinations...................130 Supporting Cancer Patients and Survivors..........132 Challenges Faced by Cancer Survivors.............132 Physical Challenges.............................................................133 Psychosocial Challenges....................................................133 Financial Challenges...........................................................135 Unique Challenges Faced by Vulnerable Patient Populations.............................................................136 Children....................................................................................136 Adolescents and Young Adults.......................................136 Older Adults...........................................................................138 Improving Health-related Quality of Life and Outcomes.......................................................138 Promoting Healthy Behaviors..........................................138 Integrating Palliative Care.................................................138 Improving Mental Health...................................................139 Delivering Care to Cancer Survivors.................141 Coordinating Care................................................................141 Supporting Caregivers.......................................................142 Envisioning the Future of Cancer Science and Medicine..............................................................143 Revolutionizing Cancer Science and Medicine...143 New Frontiers in Cancer Research..................................143 Artificial Intelligence..........................................................146 Wearable Technologies......................................................147 Tackling Difficult-to-Treat Cancers....................147 Glioblastoma.........................................................................148 Pancreatic Cancer...............................................................149 Targeting the Microbiome in Cancer Treatment............................................150 Advancing the Future of Cancer Research and Patient Care Through the Adoption of Evidence-based Policies..........................................152 Investments in Research Fuel a Healthier Future....................................................153 A Diverse Cancer Research and Care Workforce Drives Innovation.............................154 Ensuring Safe and Effective Cancer Therapies Through Regulatory Science............155 Diversifying and Decentralizing Trials............................156 Rapidly Delivering Safe and Effective Therapies to Patients..........................................................156 Addressing Cancer Drug Shortages...............................158 FDA-NCI Collaborations to Promote Innovative Clinical Research.............................................158 Advancing Policy to Strengthen Cancer Prevention and Screening Programs.................158 Leveraging Policy to Reduce Tobacco-related Illness......................................................159 Accelerating Progress Against Pediatric Cancer...................................................159 Building Health Equity by Addressing Cancer Disparities ...............................................163 Conclusion.................................................................. 166 AACR Call to Action..................................................167 References.................................................................. 168 Glossary...................................................................... 184 Appendix..................................................................... 191 Index............................................................................ 193 AACR Initiatives Accelerating Cancer Research........................................................196 AACR Cancer Progress Report 2023 iii
List of Report Graphics Figures Figure 1: Research Driving Progress Against Lung Cancer............................................................................................................. 14 Figure 2: Social Determinants of Health................................................................................................................................................ 19 Figure 3: Hallmarks of Cancer Cells........................................................................................................................................................ 25 Figure 4: The Research Cycle Advancing the Frontiers of Cancer Science and Medicine..................................................... 27 Figure 5: Inherited Cancer Risk................................................................................................................................................................ 31 Figure 6: Precision Medicine..................................................................................................................................................................... 36 Figure 7: Modifiable Cancer Risks........................................................................................................................................................... 39 Figure 8: Beyond the Lungs: Cancers Caused by Smoking Tobacco........................................................................................... 40 Figure 9: Reasons to Maintain a Healthy Weight and Stay Active................................................................................................ 42 Figure 10: What Can Cancer Screening Find and What Can Be Done?........................................................................................ 55 Figure 11: The Process Used by the U.S. Preventive Services Task Force to Develop Cancer Screening Guidelines...... 58 Figure 12: USPSTF Recommendation for Breast Cancer Genetic Testing in Women............................................................... 62 Figure 13: Phases of Clinical Trials............................................................................................................................................................ 72 Figure 14: Mastering Clinical Trial Design............................................................................................................................................... 73 Figure 15: The Pillars of Cancer Treatment............................................................................................................................................ 76 Figure 16: Milestones in the Journey to Target the Undruggable KRAS....................................................................................... 84 Figure 17: Immunotherapeutics Can Work in Many Ways................................................................................................................ 101 Figure 18: Decades of Research Breakthroughs Along the Way to Developing Immune Checkpoint Inhibitors........... 102 Figure 19: Going Deep with Immune Checkpoint Inhibitors........................................................................................................... 106 Figure 20: Common Side Effects of Immune Checkpoint Inhibitors............................................................................................. 127 Figure 21: The Gut Microbiome: A New Frontier in Cancer Prevention, Early Detection, and Treatment........................ 150 Figure 22: NIH Funding: Continuing the Momentum of Robust Increases.................................................................................. 154 Figure 23: NCI Success Rates.................................................................................................................................................................... 155 Figure 24: How Flavored Tobacco Products Contribute to Disparities......................................................................................... 162 Sidebars Sidebar 1: The Medical Research Community: Driving Progress Together................................................................................... 13 Sidebar 2: Which U.S. Population Groups Experience Cancer Disparities?................................................................................... 17 Sidebar 3: Cancer Inequities in the United States................................................................................................................................. 18 Sidebar 4: Global Burden of Cancer......................................................................................................................................................... 22 Sidebar 5: How Are Cancers and Tumors Characterized?................................................................................................................. 26 Sidebar 6: Basic Research Driving Clinical Advances Against Cancer........................................................................................... 28 Sidebar 7: What Are Genetic Alterations?.............................................................................................................................................. 30 Sidebar 8: Cancer Growth: Local and Systemic Influences................................................................................................................ 33 Sidebar 9: The National Cancer Institute’s Precision Medicine Initiatives..................................................................................... 37 AACR Cancer Progress Report 2023 iv
Sidebar 10: Percentage of U.S. Adults Who Smoked Cigarettes in 2021.......................................................................................... 41 Sidebar 11: Physical Activity Guidelines.................................................................................................................................................... 43 Sidebar 12: Making Healthy Food Choices: Nutrition Labels.............................................................................................................. 45 Sidebar 13: Guidelines for Alcohol Consumption................................................................................................................................... 46 Sidebar 14: Ways to Protect Your Skin...................................................................................................................................................... 47 Sidebar 15: Ways to Reduce Cancer Risk from Pathogens................................................................................................................. 49 Sidebar 16: HPV Vaccination Recommendations................................................................................................................................... 50 Sidebar 17: Occupation and Cancer Risk in Firefighters...................................................................................................................... 52 Sidebar 18: USPSTF-recommended Tests to Screen for Cancer........................................................................................................ 56 Sidebar 19: Benefits and Potential Harms of Cancer Screening........................................................................................................ 57 Sidebar 20: The USPSTF Grading System for Cancer Screening Guidelines.................................................................................. 59 Sidebar 21: USPSTF Guidelines for Cancer Screening.......................................................................................................................... 60 Sidebar 22: Inequities in Cancer Screening.............................................................................................................................................. 63 Sidebar 23: Evidence-based Interventions to Increase Adherence to Cancer Screening........................................................... 64 Sidebar 24: Artificial Intelligence in Early Cancer Detection............................................................................................................... 66 Sidebar 25: What Is Medical Research?..................................................................................................................................................... 69 Sidebar 26: Therapeutic Development....................................................................................................................................................... 70 Sidebar 27: Types of Clinical Trials............................................................................................................................................................... 71 Sidebar 28: Disparities in Clinical Trial Participation.............................................................................................................................. 74 Sidebar 29: Telemedicine in Cancer Care.................................................................................................................................................. 75 Sidebar 30: Disparities in Cancer Treatment............................................................................................................................................ 78 Sidebar 31: Using Surgery for Cancer Treatment................................................................................................................................... 79 Sidebar 32: Commonly Used Terms and Benchmarks in Clinical Studies....................................................................................... 80 Sidebar 33: Using Radiation in Cancer Treatment................................................................................................................................... 81 Sidebar 34: Companion Diagnostics........................................................................................................................................................... 85 Sidebar 35: The Challenge of Treatment Resistance............................................................................................................................. 87 Sidebar 36: The Challenges Posed by Rare Cancers.............................................................................................................................. 90 Sidebar 37: Recent Advances Against Blood Cancers.......................................................................................................................... 94 Sidebar 38: Key Cells of the Immune System........................................................................................................................................ 100 Sidebar 39: T Cell-based Adoptive Cell Therapy.................................................................................................................................... 116 Sidebar 40: CAR T-cell Therapies Approved by the U.S. Food and Drug Administration.......................................................... 117 Sidebar 41: Clinical Trials Testing Immunotherapy Combinations with Other Modalities.......................................................... 131 Sidebar 42: Phases of Cancer Survivorship............................................................................................................................................. 134 Sidebar 43: Fertility Preservation After a Diagnosis of Cancer......................................................................................................... 137 Sidebar 44: What Is Palliative Care?.......................................................................................................................................................... 139 Sidebar 45: Helping Patients with Cancer Through Psycho-oncology Research......................................................................... 139 Sidebar 46: Coping with Posttraumatic Stress After a Cancer Diagnosis..................................................................................... 140 AACR Cancer Progress Report 2023 v
Sidebar 47: Patient Navigation..................................................................................................................................................................... 141 Sidebar 48: Patient Reported Outcomes.................................................................................................................................................. 142 Tables Table 1: Estimated Incidence and Mortality for Selected Cancers............................................................................................... 16 Table 2: Cancer-causing Pathogens..................................................................................................................................................... 48 Table 3: Newly FDA-approved Anticancer Agents: August 1, 2022-July 31, 2023................................................................. 77 Table 4: Summary of Current Clinical Trial Practices and Recommended Changes............................................................. 157 Supplemental Tables Table 1: Surgeries for the Prevention of Cancer............................................................................................................................... 191 Table 2: Newly FDA-approved Anticancer Agents: August 1, 2022-July 31, 2023 (Extended Table).............................................................................................................. 192 AACR Cancer Progress Report 2023 vi
Steering Committee Philip D. Greenberg, MD, FAACR Chair AACR President 2023-2024 Professor & Head, Program in Immunology The Rona Jaffe Foundation Endowed Chair Investigator, Parker Institute for Cancer Immunotherapy Fred Hutchinson Cancer Center Seattle, Washington James L. Abbruzzese, MD Duke Cancer Institute Distinguished Professor of Medical Oncology Professor of Medicine Duke Cancer Institute Durham, North Carolina Ezra E. W. Cohen, MD Associate Director for Translational Science Leader of the Solid Tumor Therapeutics Research Program UC San Diego Health Moores Cancer Center San Diego, California Susan M. Domcheck, MD Director, Basser Center for BRCA Basser Professor of Oncology University of Pennsylvania Philadelphia, Pennsylvania Chyke A. Doubeni, MD, MPH Chief Health Equity Officer The Ohio State University Wexner Medical Center Associate Director for Diversity, Equity and Inclusion The Ohio State University Comprehensive Cancer Center Columbus, Ohio Ivy Elkins, MBA Lung Cancer Advocate Co-Founder, EGFR Resisters Silvia C. Formenti, MD Professor and Chair, Department of Radiation Oncology Associate Director for Translational Research, Meyer Cancer Center Weill Cornell Medicine New York, New York Margaret Foti, PhD, MD (hc) Chief Executive Officer American Association for Cancer Research® Philadelphia, Pennsylvania Thomas J. Fuchs, DrSC Chair, Windreich Department of Artificial Intelligence and Human Health Co-Director, Hasso Plattner Institute for Digital Health Dean of Artificial Intelligence and Human Health Barbara T. Murphy Professor Icahn School of Medicine at Mount Sinai New York, New York John C. Kucharczuk, MD Associate Professor of Surgery Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Ravindra Majeti, MD, PhD Director, Stanford Institute for Stem Cell Biology and Regenerative Medicine RZ Cao Professor Professor of Medicine in Hematology Stanford University Stanford, California Paul Mischel, MD Professor and Vice Chair for Research, Department of Pathology Professor, Department of Neurosurgery Institute Scholar, Sarafan ChEM-H Stanford University Stanford, California Lorelei A. Mucci, ScD, MPH Professor of Epidemiology Harvard TH Chan School of Public Health Boston, Massachusetts Padmanee Sharma, MD, PhD Professor of Genitourinary Medical Oncology Professor of Immunology Scientific Director of Immunotherapy Platform Associate VP of Immunobiology Director of Scientific Programs, James P. Allison Institute MD Anderson Cancer Center Houston, Texas Melissa A. Simon, MD, MPH Vice Chair of Research, Department of Obstetrics and Gynecology George H. Gardner Professor of Clinical Gynecology Professor of Obstetrics and Gynecology, Preventive Medicine and Medical Social Sciences Founder/Director, Center for Health Equity Transformation Founder/Director, Chicago Cancer Health Equity Collaborative Northwestern University, Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center Chicago, Illinois Alejandro Sweet-Cordero, MD Chief, Division of Pediatric Oncology Director, Molecular Oncology Initiative Benioff Professor of Children’s Health University of California San Francisco San Francisco, California Gita Thanarajasingam, MD Associate Professor of Medicine Consultant, Division of Hematology, Lymphoma Disease Group Mayo Clinic Rochester, Minnesota AACR CANCER PROGRESS REPORT 2023 AACR Cancer Progress Report 2023 vii
AACR Staff Rajarshi Sengupta, PhD Director, Scientific Research Analysis and Dissemination Philadelphia, Pennsylvania Sayyed Kaleem Zaidi, PhD Associate Director, Scientific Research Analysis and Dissemination Philadelphia, Pennsylvania Patrick A. Williams, PhD Senior Scientific Research Analyst, Scientific Research Analysis and Dissemination Philadelphia, Pennsylvania Heather Clark Lead Designer, Marketing and Creative Services Philadelphia, Pennsylvania Jenna M. Bachen Director, Creative Services Philadelphia, Pennsylvania Richard G. Buck Chief Communications Officer and Vice President Philadelphia, Pennsylvania Paul J. Driscoll, Jr Chief Marketing Officer and Vice President Philadelphia, Pennsylvania Joshua F. Goldstein Senior Director, Brand Strategy Communications Philadelphia, Pennsylvania Matt Gontarchick Assistant Director, Government Affairs Washington, DC Karen Honey, PhD Executive Editor, Cancer Immunology Research Philadelphia, Pennsylvania Benjamin Krinsky, PhD Director, Federal Government Affairs Washington, DC Eileen Loftus Senior Writer and Editor, Communications and Public Relations Philadelphia, Pennsylvania Mary Anne Mennite Executive Editor and Senior Liaison to the CEO Philadelphia, Pennsylvania Calais Prince, PhD Associate Director, Science and Health Policy Washington, DC Jon G. Retzlaff, MBA, MPA Chief Policy Officer and Vice President Washington, DC Blake Rostine Manager, Congressional Affairs Washington, DC Nicholas Warren, PhD Assistant Director, Science and Regulatory Policy Washington, DC Carrie Treadwell, MBA Director, Strategic Patient Advocacy and Engagement Washington, DC ABOUT THE AMERICAN ASSOCIATION FOR CANCER RESEARCH Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 54,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 130 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting. In addition, the AACR publishes 10 prestigious, peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual investigator grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and other policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit AACR.org. AACR Cancer Progress Report 2023 viii
We are in an era of extraordinary scientific progress against cancer. In the United States, overall cancer death rates are continuing to decline, and the number of cancer survivors has reached a record high. Breakthroughs across the spectrum of cancer science and medicine are contributing to unparalleled advances against previously intractable diseases, such as advanced lung cancer and metastatic melanoma. Thanks to the new wave of scientific discoveries and technological innovation, we are now poised to deliver transformative advances that will save even more lives from cancer. The AACR Cancer Progress Report 2023 provides a comprehensive overview of the remarkable progress we are making because of medical research, much of which is supported by federal investments in the National Institutes of Health (NIH) and the National Cancer Institute (NCI). As highlighted in the report, federal funding for medical research has enhanced our understanding of the complexities of cancer and accelerated the rate at which this knowledge is being harnessed to develop new and better approaches to preventing, detecting, diagnosing, treating, and curing cancer. Among the advances detailed in the report are the 14 new anticancer therapeutics that were approved by the U.S. Food and Drug Administration (FDA) between August 1, 2022, and July 31, 2023. Among the new treatments is the first antibody-drug conjugate, a type of molecularly targeted therapeutic, approved for treating patients with ovarian cancer harboring a specific biomarker. Another major advance in cancer medicine is the FDA approval of a molecularly targeted therapeutic specifically directed against the altered protein arising from a mutated KRAS gene, one of the most commonly mutated genes in human cancers. This remarkable achievement—the drug being only the second of its kind to receive FDA approval—was made possible by decades of laboratory and clinical research. As we continue to discover the molecular and cellular underpinnings of the collection of diseases we call cancer, there will be more groundbreaking discoveries that further advance the frontiers of precision cancer medicine. As showcased in the report, decades of basic research in the field of immunology have led to a surge in the impact of cancer immunotherapy, the newest pillar of cancer treatment that has revolutionized patient care. The use of immune checkpoint inhibitors (ICI), which are immunotherapeutics that work by releasing brakes on the natural cancer-killing power of the immune system, has expanded at an unprecedented pace over the past decade. In January 2013, there was only one FDAapproved ICI for treating just one cancer type. As of July 31, 2023, there were 11 ICIs approved by FDA, and at least one ICI has been approved for treating 20 different types of cancer and any type of solid tumor characterized by the presence of specific molecular signatures, or biomarkers. CAR T-cell-based immunotherapies, which are currently approved for an array of hematologic cancers, have ushered in a new era of personalized medicine because they are generated by the genetic engineering of a patient’s own immune cells to attack his or her cancer cells. Expanding our knowledge about the immune system and how it interacts with cancer cells, and facilitating the convergence of experts from an increasingly diverse array of disciplines, will create even more opportunities for pioneering advances in immunotherapy for the benefit of patients around the world. Despite these significant strides against the disease, we must continue our quest for newer and more innovative methods to prevent and cure cancer while improving the quality of life of our patients. This urgent need is underscored by the sobering reality that nearly 2 million American will be diagnosed with cancer in 2023. This number is predicted to increase considerably in the coming decades because cancer is largely a disease of aging, and the segment of the U.S. population age 65 and older is growing. Therefore, it is critical to implement newer and more effective strategies for cancer prevention, early detection, diagnosis, and treatment. Moving forward, we must also ensure that everyone benefits from the groundbreaking advances against cancer. As highlighted in this report, racial and ethnic minorities and other medically underserved populations shoulder a disproportionate burden of cancer. Participation of patients from these population groups in clinical trials that are testing lifesaving new anticancer therapeutics continues to be disappointingly low. We must adopt new approaches to inform, educate, and encourage cancer patients to enroll in clinical trials so that researchers can identify the most efficacious approaches to help all patients. As a scientific organization whose core values include diversity, equity, and inclusion, AACR is fiercely committed to addressing all inequities in cancer research and patient care and to ensuring sociodemographic diversity in the cancer workforce so that it is reflective of the patient population it serves. Looking to the future, we strongly believe that we have never been in a better position to take lifesaving cancer science A Message from AACR AACR Cancer Progress Report 2023 1
from the bench to the clinic. Thanks to bipartisan leadership in Congress that has delivered steady and significant annual funding increases for NIH and NCI, we now have the scientific knowledge, cutting-edge technologies, and capability to deliver unprecedented advances to all cancer patients. As the first and largest professional organization in the world dedicated to advancing all areas of cancer science and medicine, AACR is thrilled to work alongside the administration and complement the NCI’s National Cancer Plan to meet the goal of the reignited Cancer Moonshot of reducing the cancer death rate by at least half by 2047. To address the nation’s cancer mission and its challenges at the earliest possible time, AACR launched the AACR Cancer Centers Alliance on September 13, 2023. This formal partnership with the nation’s cancer centers will serve as a catalyst to marshal their resources and collaborate directly, effectively, and synergistically to propel new lifesaving cures for the millions of people whose lives are touched by cancer. To maintain the momentum against cancer, we must ensure that medical research remains a national priority for our policymakers. Notably, the return on the federal investments in medical research has been extraordinary. For example, in the last 40 years, U.S. patients with cancer have collectively gained nearly 14 million years of life because of NCI-funded cancer research. Therefore, AACR urges Congress to continue to support robust, sustained, and predictable annual increases in the budgets of NIH and NCI, and to provide consistent and sufficient annual funding for the Cancer Moonshot, FDA, and Centers for Disease Control and Prevention (CDC). These actions will further advance the frontiers of cancer science and medicine and save more lives from cancer. Philip D. Greenberg, MD, FAACR AACR President Margaret Foti, PhD, MD (hc) AACR Chief Executive Officer AACR Cancer Progress Report 2023 A Message from AACR 2
Executive Summary Unprecedented progress in medical research is increasing our understanding of the collection of diseases we call cancer and is driving remarkable improvements in cancer prevention, early detection, diagnosis, and treatment. These advances are made possible by investments in NIH, NCI, FDA, and CDC by the U.S. federal government. As the first and largest professional organization in the world dedicated to preventing and curing all cancers, AACR has been and continues to be a catalyst for scientific breakthroughs that save and enhance the lives of patients with cancer. AACR is also committed to increasing public understanding of cancer and advocating for increased federal funding for medical research. The annual AACR Cancer Progress Report to Congress and the American public is a cornerstone of AACR’s educational efforts. This thirteenth edition of the report highlights how research continues to extend and improve the lives of Americans, including the lives of the eight courageous individuals featured in the report and their family members who have shared their experiences with cancer. It also underscores how unwavering, bipartisan support from Congress, in the form of robust and sustained annual increases in funding for NIH, NCI, FDA, and CDC, is urgently needed if we are to realize our vision of eradicating cancer for all populations. Cancer in 2023 The remarkable progress being made against cancer is resulting in a steady reduction in cancer death rates, and a consistent rise in the number of people who live longer and fuller lives after a cancer diagnosis. In fact, the overall U.S. cancer death rate has fallen by 33 percent between 1991 and 2020, a reduction that translates into averting an estimated 3.8 million deaths from cancer. The reduction in overall cancer mortality is driven largely by the decline in the U.S. lung cancer death rate, the pace of which has accelerated in recent years because of reduction in smoking and advances in early detection and treatment. Additionally, the reduction in death rates for melanoma, colorectal cancer, prostate cancer, and female breast cancer has contributed to the progress against overall U.S. cancer mortality. Notably, among U.S. children (14 years or younger) and adolescents (15 to 19 years), overall cancer death rates have declined by 70 percent and 64 percent, respectively, over the past five decades, driven largely by improvements in treatment. Despite significant advances, cancer continues to be an ongoing public health challenge in the United States and around the world. In the United States alone, it is estimated that nearly 2 million new cancer cases will be diagnosed in 2023. Among the challenges we face is the fact that the advances we have made have not been uniform for all types and stages of cancer. For example, while the death rates for many of the commonly diagnosed cancers in the United States—including breast, lung, and prostate cancer—have been declining, those for other forms of cancer—most notably pancreatic and uterine cancer—have been increasing. Moreover, the burden of cancer is shouldered disproportionately by certain segments of the population, including racial and ethnic minorities and patients from other medically underserved populations. These disparities are driven by complex and interrelated factors, called social determinants of health. 18+ MILLION SURVIVORS (5.4% OF THE POPULATION) 3 MILLION SURVIVORS (1.4% OF THE POPULATION) 2022 1971 "All of the advances in cancer research are coming together to make therapies increasingly precise so we can improve the quality of life of patients." Philip D. Greenberg, MD, FAACR AACR President, 2023-2024 AACR Cancer Progress Report 2023 3
The burden of cancer and its economic toll, both on individuals and on the U.S. health care system, are expected to rise in the coming decades, underscoring the urgent need for more research to accelerate the pace of progress against cancer. The progress highlighted in this report was made as a direct result of the cumulative efforts of individuals working across the spectrum of medical research and the support from the federal government. Public sector funding from NIH and NCI directly contributes to patient benefit such as through the development of lifesaving anticancer therapeutics. Continued federal investments in NIH, NCI, FDA, and CDC will help the medical research community maintain the momentum of scientific and technological innovation, accelerate the pace of progress against cancer, and ensure that we achieve the President’s Cancer Moonshot goal of reducing U.S. cancer death rates by 50 percent by the year 2047. Understanding the Path to Cancer Development Decades-long research in basic, translational, clinical, and population sciences, and the breakthroughs stemming from it, have advanced our understanding of cancer development. Insights gleaned from this knowledge have revealed cancer as a collection of diseases that are characterized by unchecked cell multiplication. We now understand that different cancer types share many so-called hallmarks or characteristics. These hallmarks are primarily acquired through alterations in the genetic material of normal cells. The nature and the type of genetic alterations determine when cancer is initiated, how fast it progresses, and where in the body it spreads. Research has shown that there are two types of genetic mutations associated with cancer: inherited and somatic. Inherited mutations are passed on from parents to their progeny and contribute to about 10 percent of all cancer cases. Most cancers are caused by somatic mutations. Somatic mutations are acquired throughout a person’s lifetime and can arise in multiple ways, including from errors made during cell division, smoking, certain viral infections, exposure to UV radiation, and/or exposure to mutagens or other cancer-causing chemicals. Although cancer is a genetic disease at a fundamental level, transformation of normal cells into cancer cells, accumulation of cancer cells to form tumors, and spread of tumors to distant sites are all complex, multistep processes that are further influenced by changes outside the cell. As the disease progresses, cancer cells acquire additional characteristics that give them the ability to manipulate their cellular and molecular environment. The resultant tumor microenvironment can affect how the tumor grows and spreads, and cancer cells can reciprocally influence the tumor microenvironment to promote their survival. A technological revolution in our ability to study cancer at the levels of single cells and molecules has led to important insights, one of which is that each patient’s cancer is unique, thus providing the basis for precision medicine. Also called personalized medicine, precision medicine is broadly defined as treating patients based on molecular characteristics that distinguish them from other individuals with the same disease. As ongoing research continues to unravel the mechanisms of cancer onset and progression, researchers are already leveraging existing knowledge to develop more effective, personalized anticancer therapeutics and improve health outcomes for patients with cancer. Reducing the Risk of Cancer Development Research in basic, translational, and population sciences has broadened our understanding of the factors that increase an individual’s risk of developing cancer. Many of these risk factors are modifiable, such as reducing tobacco use, avoiding an In the United States, patients with cancer have collectively gained nearly 14 million years of life since 1980 as a result of NCIfunded clinical trials. HALLMARKS OF CANCER CELLS Spread to other parts of the body Multiply limitlessly Increase blood vessel formation toward tumor Evade the immune system Increase nutrient and oxygen supply to the tumor Escape cell death Grow uncontrollably Accumulate changes in the genetic material AACR Cancer Progress Report 2023 Executive Summary 4
unhealthy diet, lowering physical inactivity, lowering exposure to UV radiation, limiting alcohol consumption, and preventing pathogenic infections. It is estimated that 40 percent of all cancer cases in the United States are attributable to preventable causes. The development and implementation of public education and policy initiatives designed to eliminate or reduce exposure to preventable causes have reduced cancer incidence, morbidity, and mortality in the United States. Unfortunately, while the prevalence of some risk factors like tobacco use is on the decline, the rise in prevalence of other risk factors such as obesity threatens to reverse the significant progress against cancer that has been made in the last five decades. Therefore, it is essential that all stakeholders work together to enhance the dissemination of our current knowledge to reduce cancer risk and implement evidence-based policies and programs that minimize the incidence, morbidity, and mortality of cancer attributable to preventable causes. Certain cancer risk factors are not always easy to avoid. These include carcinogens and pollutants encountered in the environment. Hormonal factors that result from normal physiology can also increase or decrease the risk of developing certain types of cancers. Furthermore, occupational or life stressors, such as chronic stress, lack of sleep, and night shift work, increase a person’s risk of developing certain types of cancers. As we learn more about environmental and occupational cancer risk factors and identify segments of the U.S. population who are exposed to these factors, new and equitable policies need to be developed and implemented to reduce cancer risk and improve the health of all populations. Screening for Early Detection Cancer screening means checking for the disease, or for abnormal cells that may become cancerous, in people who have no signs or symptoms of cancer. Cancer screening can help detect aberrations at the earliest possible stage during cancer development when they are successfully treatable, with a higher likelihood of being cured. The overarching goal of recommended screening is to reduce the burden of cancer at the population level. Cancer screening recommendations are developed for individuals who are at an average or higher-than-average risk of being diagnosed with cancer. Key considerations that determine who should receive screening and for which cancer include gender and age, as well as genetic, environmental, behavioral, and social influences. In the United States, the U.S. Preventive Services Task Force (USPSTF)—an independent, volunteer panel of national experts in disease prevention and evidence-based medicine— has recommendations for individuals who are at an average risk of being diagnosed with breast, cervical, colorectal, or prostate cancer. The USPSTF recommends that people who currently smoke or have a history of smoking, i.e., individuals who are at a high risk of being diagnosed with the disease, receive lung cancer screening. Despite the evidence that cancer screening saves lives, systemic and structural barriers disproportionately limit the access of medically underserved populations to routine cancer screening. Researchers are using evidence-based interventions—such as comprehensive public health campaigns and culturally tailored strategies—to reduce these barriers, but more work is needed to ensure that all eligible individuals have equitable access to routine cancer screening and follow-up testing if findings of the screening test are abnormal. Use of artificial intelligence (AI) to aid clinicians in cancer detection, and of liquid biopsy to detect multiple types of cancer from a single test, is an exciting new frontier that holds enormous potential for improving early detection of cancer. In recent years, FDA has approved several AI-assisted medical devices to aid clinicians in cancer diagnosis. However, a cautious approach to using AI in cancer care is warranted to avoid exacerbating inequities that can result from the fact that much of the data used to train current AI-driven models 1965 2021 Cigarette Smoking Rates Among U.S. Adults 42% 11.5% In May 2023, USPSTF issued a draft recommendation for breast cancer screening, lowering the age of eligible individuals from 50 to 40. Researchers estimate that the revised recommendation could save 19 percent more lives from breast cancer. Executive Summary AACR Cancer Progress Report 2023 5
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