AACR Cancer Progress Report 2015
Authors: José Baselga, Nina Bhardwaj, Lewis C. Cantley, Ronald DeMatteo, Raymond N. DuBois, Margaret Foti, Susan M. Gapstur, William C. Hahn, Lee J. Helman, Roy A. Jensen, Electra D. Paskett, Theodore S. Lawrence, Stuart G. Lutzker, Eva Szabo
Journal: Clinical Cancer Research (2015)

*These authors contributed to the devlopment and review of this manuscript but are unable to endorse the request for NIH funding.On Sept. 20, 2011, the American Association for Cancer Research (AACR) released its inaugural AACR Cancer Progress Report to commemorate the advances in biomedical research that transformed cancer care in the 40 years following the signing of the National Cancer Act of 1971. During this period, biomedical research dramatically increased our understanding of the collection of diseases we call cancer, including the discovery that most cancers are caused by genetic mutations. This laid the foundation for the era of precision medicine, and by Jan. 1, 2011, 20 therapeutics targeting specific molecules involved in cancer had been approved by the U.S. Food and Drug Administration (FDA). Among these therapeutics are some that target cancer-specific molecules, some that target the blood vessel growth that supports tumor development, and some that stimulate a patient's immune system to eliminate their cancer.As highlighted in the AACR Cancer Progress Report 2015, progress against cancer has continued at a spectacular pace since the start of 2011. In fact, during the five years of publishing the AACR Cancer Progress Report, the number of FDA-approved therapeutics targeting specific molecules involved in cancer more than doubled, reaching 52 therapeutics by July 31, 2015. For some forms of cancer, including melanoma and chronic lymphocytic leukemia, we now have five or more of these new therapeutics, which–as a result of their increased precision–have fewer adverse side effects compared with the traditional treatments that have been the mainstay of cancer care for decades.This rapid surge in the number of increasingly precise anticancer therapeutics was powered by research, and the cumulative knowledge of the complexities of cancer continues to be the foundation of new advances across the clinical cancer care continuum. Discoveries in the fields of cancer genomics and immunology have been particularly fruitful and have firmly established two new pillars of cancer care: precision therapy and immunotherapy. These exciting fields of research also show immense promise for the future.Advances in cancer genomics are fueling an expansion in the clinical use of genomic information to make otherwise unexpected treatment decisions for patients with a wide range of cancer types, like the four patients featured in the Transforming Lives One Sequence at a Time section of the AACR Cancer Progress Report 2015 (p. 29). Genomic sequencing of two of these patients' cancers revealed the presence of BRAF gene mutations commonly found in melanoma, and a BRAF-targeted therapeutic approved by the FDA for treating BRAF-mutant melanoma has been transforming the lives of these patients for more than a year.Precision medicine stories like these are becoming more common because the explosion in our understanding of the biology of cancer is making it increasingly possible to identify the most appropriate therapy for a patient. Our increased knowledge of cancer is also enabling the more precise use of radiotherapy and traditional chemotherapy, as well as cancer prevention strategies tailored for maximal effectiveness.The dedicated efforts of researchers working throughout the cycle of biomedical research in the United States and around the world are making possible continual progress against cancer. The AACR is encouraged by the fact that 85 percent of American voters recognize that progress is being made against cancer, according to results from a 2015 national survey conducted on behalf of the organization by Hart Research Associates and Public Opinion Strategies. This progress is powering revolutionary advances in cancer care, and the AACR is grateful to the 13 courageous beneficiaries of some of these advances who shared their personal experiences with cancer in the AACR Cancer Progress Report 2015. These stories, coupled with the advances described in the report, inspire great hope for a future in which cancer no longer threatens the lives of millions.Unfortunately, our ability to fully capitalize on our ever-growing knowledge of cancer is at risk. This is because federal investments in the National Institutes of Health (NIH) and its largest component institute, the National Cancer Institute (NCI), which spur much of the progress made against cancer, have stagnated. Since 2004, the budgets for the NIH and NCI have not kept pace with inflation, resulting in the NIH losing approximately 25 percent of its ability to fund lifesaving biomedical research. On top of these losses due to inflation, direct budget cuts in 2011 and 2013 slashed federal support of the NIH and NCI.Investments in the federal agencies that are vital for powering progress against cancer also fuel the economy and help the United States to maintain its important position as the global leader in biomedical research. Therefore, reduced federal investments in the NIH and NCI jeopardize not only future lifesaving biomedical research, but also economic development and U.S. leadership in the field.The AACR urges Congress and the administration to implement a strategy for providing annual budget increases of at least 7 percent for the NIH, NCI, and FDA beginning in FY 2016 and thereafter. This call to action is in line with the opinion of the majority of American voters, because three out of every four voters favor increasing federal funding for cancer research, according to results from the 2015 AACR survey. Thus, we urge all members of the AACR and, indeed, all Americans to join us in calling on Congress and the administration to prioritize the growth of the NIH, NCI, and FDA budgets through annual funding increases that are robust, sustainable, and predictable. There is no time to waste when, in the United States alone, we are losing one person every minute of every day to the devastating collection of diseases we call cancer.Research powers progress against cancer by increasing our understanding of the collection of diseases we call cancer and by allowing us to translate this knowledge into new and increasingly precise ways to prevent, detect, diagnose, treat, and cure some of these diseases.Much of the research that powers progress against cancer is funded by the U.S. federal government through the National Institutes of Health (NIH), in particular its largest component institute, the National Cancer Institute (NCI). Additionally, federal funding of the U.S. Food and Drug Administration (FDA) helps speed the delivery of safe and effective treatments, such as anticancer therapeutics, to the patients who need them.As the oldest and largest cancer organization in the world dedicated to advancing every aspect of cancer research, from basic science to translational research to clinical research and population science, the American Association for Cancer Research (AACR) is committed to increasing public understanding of cancer and the importance of cancer research to public health, as well as to advocating for increased federal funding for the NIH, NCI, and FDA. These investments will contribute markedly to the goal of saving more lives from cancer.The annual AACR Cancer Progress Report to Congress and the American public is a cornerstone of the AACR's educational and advocacy efforts. This fifth edition of the report chronicles how research continues to transform lives, like the lives of the 13 courageous individuals featured in the report who have shared their experiences with cancer. It also contains a special section showcasing the advances made against cancer in the five years of publishing the report. The progress against cancer highlighted in the report underscores how unwavering, bipartisan support from Congress and the administration, in the form of sustained increases in funding for the NIH, NCI, and FDA, are vital if we are to continue to make progress for the benefit of families everywhere.Research is the foundation of new and better approaches to cancer prevention, detection, diagnosis, and treatment, which are driving down overall U.S. cancer death rates and increasing the number of people who are living longer, higher-quality lives after a cancer diagnosis.Even though extraordinary advances have been made, cancer continues to exert an enormous global toll. In 2015 alone, it is estimated that about 8.9 million people worldwide will die from some form of cancer, 589,430 of whom are individuals living in the United States. Moreover, these numbers are projected to increase dramatically in the coming decades if new and better ways to prevent, detect, diagnose, and treat cancer are not developed.Fueling the anticipated increase in cancer deaths will be a rise in the number of cancer diagnoses, which will, in turn, drive up the costs of cancer. In the United States alone, it is estimated that the direct medical costs of cancer care will rise to $156 billion in 2020, from nearly $125 billion in 2010. When these costs are compared to the total NCI budget for fiscal year 2015, which is just $5 billion, it is clear that research that spurs lifesaving progress against cancer is a wise national investment.To celebrate the fifth edition of the AACR Cancer Progress Report, a special feature is included that highlights the incredible advances that have been made against cancer in the five years of publishing the report. Discoveries in the fields of cancer genomics and immunology have spurred particular progress, including the rapid expansion of two new pillars of cancer care: precision therapy and immunotherapy.Information generated by the field of cancer genomics is the foundation of precision therapy, which is revolutionizing the standard of cancer care from a one-size-fits-all approach to one in which the best therapeutic strategy for a patient is determined by an increasingly deep understanding of the patient and his or her tumor. This information is being used not only to expand the repertoire of precision therapeutics, but also to identify additional patients who could benefit from the precision therapeutics that we already have–like the four patients in the Transforming Lives One Sequence at a Time highlight (see p. 29)–and to increase the precision with which traditional chemotherapy and immunotherapy are utilized.An increased understanding of the role of genetic alterations in developing cancer is also the foundation on which changes are being made in the way that many cancer clinical trials are conducted and regulated. These changes are essential if we are to continue to move precision medicine forward more rapidly than ever before.Many cases of cancer could be prevented by eliminating or reducing exposure to factors that increase a person's risk of developing cancer.Past U.S. public education and policy initiatives have been successful in reducing cancer morbidity and mortality through prevention. However, given that an estimated 50 percent of the 589,430 U.S. cancer deaths expected to occur in 2015 are attributable to preventable causes, it is clear more needs to be done.Most prominent among the preventable causes of cancer are tobacco use, obesity, lack of physical activity, exposure to ultraviolet light from the sun or tanning devices, and failure to use or comply with interventions that treat or prevent infection with cancer-associated pathogens, such as cancer-causing strains of human papillomavirus (HPV).Unfortunately, some individuals continue to expose themselves to preventable causes of cancer despite public education and policy initiatives. Moreover, not all cancer risk factors are avoidable. As a result, cancer screening strategies that can identify a precancer or cancer early in development, when it can be more easily and successfully intercepted, are an important part of health care. However, given that each person has his or her own unique risks for developing each type of cancer, everyone should consult with his or her health care practitioners to develop a personalized cancer screening plan.As we develop and implement new strategies that pair increased molecular understanding of cancer development with knowledge of an individual's unique cancer risk profile, we will move closer to a new era of precision cancer prevention and interception.The dedicated efforts of researchers working throughout the cycle of biomedical research fuel advances across the clinical cancer care continuum that are transforming lives in the United States and worldwide.As a result of research advances, the FDA approved nine new anticancer therapeutics, one new cancer prevention vaccine, and one new cancer screening test in the 12 months leading up to July 31, 2015. During this time, the FDA also approved new uses for six previously approved anticancer therapeutics and one imaging agent.Four of the new anticancer therapeutics approved by the FDA target specific molecules involved in cancer and are referred to as molecularly targeted therapeutics. They are part of the precision medicine revolution in cancer care that is transforming the lives of patients like Patty Klein, Janet Klein, and Lori Cuffari (p. 72, 76, and 80, respectively).Four of the new anticancer therapeutics approved by the FDA are immunotherapeutics that are yielding remarkable and durable patient responses, as illustrated in the report by the experiences of Donna Fernandez, Elizabeth Buell-Fleming, and Sergio Ramirez (p. 86, 90, and 92, respectively). This is the largest number of immunotherapeutics approved in a 12-month period since the first AACR Cancer Progress Report was published in 2011, highlighting how this powerful form of cancer treatment has emerged as a key pillar of cancer care.Even though significant progress has been made in precision therapy and immunotherapy for the treatment of cancer, surgery, radiotherapy, and traditional chemotherapy continue to form the foundation of treatment for almost all patients, as they did for Congresswoman Rosa DeLauro and Congressman Tom Marino (p. 66 and 68, respectively). However, the more we learn about the molecular makeup of individual patients and their tumors, the more precisely we will be able to use these treatment strategies so that each patient's treatment is only as aggressive as is necessary for it to be effective.Cancer genomics research is central to the precision medicine revolution that has been improving the lives of an increasing number of patients with cancer, particularly during the past five years. However, many researchers, including AACR President José Baselga, MD, PhD (p. 102), think that the best is yet to come, and that as we look to the future, the pace of progress in precision medicine will continue to accelerate.Increased deployment of cancer genomics research promises not only to increase the number of potential targets for the development of novel precision anticancer therapeutics, but also to identify markers of response and resistance to all forms of treatment. The power of this information to transform patient care could be dramatically enhanced by pairing knowledge of genetic markers of response and resistance with emerging technologies, often referred to as liquid biopsies.Federal investments in the NIH, NCI, and FDA have powered extraordinary progress against cancer by catalyzing scientific discovery and enabling the translation of discoveries into advances across the continuum of clinical cancer care. Progress in the area of precision medicine has been particularly striking, although there are many challenges to overcome if we are to realize our goal of expanding precision medicine to all forms of cancer prevention, detection, diagnosis, and treatment.First and foremost, we must continue to increase our understanding of the biology of cancer and to develop new approaches to translating this knowledge into health care advances that will save lives. To do this, we must prioritize and increase federal funding for biomedical research, cancer research, and the FDA. Only by investing in research talent, tools, and infrastructure; supporting regulatory science initiatives; and increasing patient involvement in precision medicine initiatives will we be able to accelerate the pace of progress and realize our goal of preventing and curing cancer.Achieving these goals will require Congress to work in a bipartisan fashion to enact a broad-based budget deal that raises the discretionary funding caps for FY 2016 and beyond. This would allow our nation's policymakers to invest in priority areas, such as biomedical research, cancer research, and regulatory science, which will speed innovation and accelerate the pace of development of products that are safe, effective, and ultimately advance public health.By committing to provide the NIH, NCI, and FDA with annual funding increases that are robust, sustained, and predictable, we will transform cancer care, spur innovation and economic growth, maintain our position as the global leader in science and biomedical research, and, most importantly, bring hope to cancer patients and their loved ones.Research improves survival and quality of life for millions of individuals around the world by catalyzing the development and implementation of new and better ways to prevent, detect, diagnose, treat, and cure some of the diseases that we call cancer.It takes many years of hard work by individuals from all segments of the biomedical research community to bring a new medical product from initial research discovery through approval by regulatory agencies and into the clinic (see sidebar on The Biomedical Research Community, p. 9). Among the new medical products approved by the U.S. Food and Drug Administration (FDA) between Aug. 1, 2014, and July 31, 2015, were nine new anticancer therapeutics, one new cancer prevention vaccine, and one new cancer screening test (see Table 1, p. 10). During this period, the FDA also approved new uses for six previously approved anticancer therapeutics and one imaging agent. Advances such as those listed in Table 1 (p. 10) help ensure that, year after year, overall U.S. cancer death rates continue to decrease (2) and that the number of people who survive their cancer continues to rise. In fact, in the United States alone, the percentage of the population living with, through, or beyond a cancer diagnosis has more than tripled since 1971 (3-5).The significant progress that has been and continues to be made against cancer is the result of investments from governments, philanthropic individuals and organizations, and the private sector the world over. In the United States, federal investments in biomedical research, cancer research, and the FDA are of particular importance. The majority of U.S. federal investments in biomedical research are administered through the 27 component institutes and centers of the National Institutes of Health (NIH), the largest of which is the National Cancer Institute (NCI) (see sidebar on The National Institutes of Health by the Numbers, p. 11). Continued progress against cancer requires robust, sustained, and predictable growth in funding of lifesaving biomedical research from all sources.We have made tremendous progress against cancer—for example, the U.S. five-year relative survival rate for all cancers combined increased from 49 percent in the mid-1970s to 68 percent in 2010 (6). In spite of this progress, this collection of diseases continues to exert a devastating toll on the global population. In fact, it is predicted that about 8.9 million people worldwide will die from some form of cancer in 2015 (7), 589,430 of these individuals in the United States (6) (see Table 2, p. 12). One of the reasons that cancer continues to be an enormous public health challenge is that advances have not been uniform for all types of cancer (see Table 3, p. 14). For example, although death rates for most types of cancer have been declining in the United States since the early 1990s, those for adults diagnosed with liver or pancreatic cancer rose 2.5 percent and 0.3 percent per year, respectively, from 2007 to 2011 (6). Overall five-year relative survival rates for U.S. adults with these two types of cancer are also very low, at 17 percent for liver cancer and 7 percent for pancreatic cancer, in stark contrast to the overall five-year relative survival rates for women with invasive breast cancer and men with prostate cancer, which are 89 percent and almost 100 percent, respectively (6). Another reason that cancer continues to be a challenge is that advances have not been uniform for all patients with a given type of cancer. Five-year relative survival rates vary not only with stage at diagnosis, but also among different segments of the population (see sidebar on Cancer Health Disparities in the United States, p. 15).The reality is that cancer will continue to pose challenges for researchers, clinicians, and patients in the coming decades unless more effective strategies for cancer prevention, early detection, and treatment are developed. Given that cancer is primarily a disease of aging (12), and that the portion of the U.S. population age 65 and older is expected to double in size by 2060 (13), it is anticipated that the number of new cancer cases diagnosed each year in the United States will increase dramatically (7). In fact, it is estimated that in 2035, there will be almost 2.4 million new cases of cancer diagnosed in the United States. Also contributing to the projected increase are the continued use of cigarettes by 18 percent of U.S. adults (14) and high rates of obesity and physical inactivity, both of which are linked to an increased risk for several types of cancer (15, 16).A rise in the number of U.S. cancer cases will lead directly to an increase in the number of cancer deaths, and in the near future cancer is expected to overtake heart disease as the country's leading cause of death (17).These challenges are not unique to the United States; they are also global problems (see sidebar on Cancer: A Global Challenge). Thus, it is imperative that the global biomedical research community collaborates to address cancer incidence and mortality, and spur continued advances against cancer.Cancer exerts an immense global toll not only through the number of lives it affects each year, but also as a result of its substantial economic impact. It is estimated that the 13.3 million cases of cancer diagnosed worldwide in 2010 cost $290 billion in that year alone (18) (see Figure 1). With the number of cancer cases projected to rise dramatically in the next few decades, so too will the costs. In fact, it is estimated that the 21.5 million new cases of cancer projected to be diagnosed in 2030 will cost $458 billion (18). In the United States alone, it is estimated that the direct medical costs of cancer care in 2010 were nearly $125 billion, and that these costs will likely rise to $156 billion in 2020 (19). These costs stand in stark contrast to the NIH budget for fiscal year (FY) 2015, which is $30.3 billion.Given the increasing economic and personal burden of cancer, it is clear that more research is required if we are to continue to make new advances against cancer. In the United States, most biomedical research, as well as the federal regulatory agency that assures the safety and efficacy of advances—the FDA—is supported by funds from the federal government. Therefore, it is imperative that Congress and the administration increase investments in the federal agencies that are vital for fueling progress against cancer, in particular the NIH, NCI, and FDA.Cancer is not one disease; it is a collection of many diseases that arise when the processes that control the multiplication and life span of normal cells go awry.As humans develop, we grow, through extensive cell multiplication, from a single cell to an estimated 37.2 trillion cells in an adult body (20). When a person matures, the pace of cell multiplication slows. In adults, normal cells primarily multiply only to replace cells that die either due to exposure to a variety of external factors or naturally as a result of normal cellular wear and tear, which is related to the number of times the cell has multiplied.When the processes that control the multiplication and life span of normal cells go awry, the cells start multiplying uncontrollably, fail to die when they should, and begin to accumulate. In body organs and tissues, these cancerous cells form a tumor mass, and in the blood or bone marrow, they crowd out the normal cells.Without medical intervention, over time, some cancerous cells gain the ability to invade local tissues, and some spread, or metastasize, to distant sites. The progression of a cancer to metastatic disease is the cause of most cancer-related deaths.Changes, or mutations, in the genetic material of cells are the primary cause of cancer initiation and development. Not all mutations contribute to cancer development, but the greater the chance that a cell will acquire a mutation, the greater the chance that the cell will acquire a mutation that will cause cancer. The identity, order, and speed at which a cell acquires genetic mutations determine the length of time it takes for a cancer to develop and are influenced by numerous interrelated factors (see sidebar on Why Me? Why This Cancer? p. 19).Cancer develops largely as a result of the accumulation of mutations in the genetic material inside a cell (see sidebar on Genetic and Epigenetic Control of Cell Function). A mutation is a change in the type or order of the four deoxyribonucleic acid (DNA) units, called bases, that make up the genetic material of a cell. The sequence of DNA bases determines what proteins are produced by a cell and how much of each protein is produced, thereby defining cellular function. Many different types of mutation can lead to cancer, largely by altering the amount or function of certain proteins (see sidebar on Genetic Mutations, p. 21), although it is important to note that not all mutations result in cancer.Most cancer cells have not only numerous genetic mutations, but also profound abnormalities in their epigenomes when compared with normal cells of the same tissue. In many cases, epigenetic alterations and genetic mutations work in conjunction to promote cancer development. Of immense therapeutic interest is the discovery that although genetic mutations are permanent, some epigenetic abnormalities may be reversible. In fact, the FDA has already approved six therapeutics that cause changes in the epigenome (see Targeting the Epigenome, p. 82).Genetic mutations underpin cancer initiation and development in most cases. However, interactions between cancer cells and their environment—known as the tumor microenvironment—as well as interactions with systemic factors, also play an important role in cancer development (see sidebar on Cancer Growth: Local and Global Influences, p. 22). Therefore, developing a more comprehensive, whole-patient understanding of cancer has the potential to provide novel approaches to cancer prevention and treatment.Research has significantly increased our knowledge of the processes by which cancer starts, progresses, and results in disease. It also has expanded our ability to exploit this knowledge to develop new and better approaches to cancer prevention, detection, diagnosis, and treatment. Most of the new treatments are more precise than traditional therapies, providing patients with not just longer, but also higher-quality lives, and researchers are beginning to use the same precision strategy to develop new cancer prevention and interception interventions (see Special Feature on Five Years of Progress Against Cancer, p. 23).In the United States, the research that fuels advances against cancer is largely supported by the NIH and NCI. Given that continued progress will be made only through additional research, it is vital that the administration and Congress increase investments in the NIH and NCI, as well as the FDA, which assures the safety and efficacy of advances.To celebrate the fifth edition of the AACR Cancer Progress Report, included here is a special feature in which we highlight advances that have been made against cancer in the five years of publishing the report.The year 2011 marked the 40th anniversary of the signing of the National Cancer Act of 1971, which focused the nation's efforts and attention on the fight against cancer. Much changed between 1971 and 2011, and the AACR commemorated the amazing advances in cancer research made during that time with the publication of its inaugural AACR Cancer Progress Report.In the four decades after 1971, we went from the concept that cancer is a single disease caused by viruses to the understanding that cancer is a vast collection of diseases, some of which are indeed caused by chronic infection with certain viruses, united by overgrowth of cells (see Prevent Infection With Cancer-causing Pathogens, p. 46). More important, however, was the discovery that cancer arises from a myriad of genetic changes within cells that accumulate with time (see Developing Cancer, p. 18).That discovery, coupled with advances in biology, chemistry, physics, and technology, set the stage for the new era of precision medicine. In fact, by Jan. 1, 2011, 20 therapeutics targeting specific molecules involved in the development and progression of cancer had been discovered and approved for patient benefit. Included in this list are not only therapeutics that target cancer-specific molecules, but also those that target the blood vessel growth that supports tumor development and some immunotherapeutics.As described in this Special Feature on Five Years of Progress Against Cancer, much has changed since Jan. 1, 2011.Powered by fundamental research, our understanding of the inner workings of cancer has continued to explode. As we have learned more abou