Envisioning the Future of Cancer
Groundbreaking improvements in treatment and prevention have led to a 27% decrease in cancer mortality in the United States over the past 25 years. These improvements are the result of the critical investments our country has made in cancer research.
More recent discoveries across multiple disciplines are fueling new paradigms that were once unimaginable, such as:
- Therapies that unleash the power of a person’s immune system to attack their cancer
- Agents that target previously “undruggable” proteins driving cancer development and growth
- Noninvasive molecular tests to detect precancers and early cancers
- Vaccines to prevent cancers not associated with infection
Despite this progress, too many cancers are not prevented, detected early, or treated successfully. In addition, cancer survivors often suffer a diminished quality of life due to the harmful effects of their treatment and are at risk of another cancer. Although more research is needed to fully address these issues, more can be done right now to reduce the burden of cancer further by better implementing known and effective cancer prevention, screening, and treatment strategies.
Recent discoveries across multiple disciplines are fueling new paradigms that were once unimaginable.
We know that cancer is not one disease but many hundreds of diseases. Continued progress can be achieved through NCI’s overarching strategy of supporting a broad portfolio of research, which includes further investigation of the basic biological mechanisms of cancer, translating the knowledge gained into new tools and treatments, and disseminating those innovations into clinical practice.
The three topics discussed in depth in this Annual Plan and Budget Proposal—the immune system and microbiome, artificial intelligence, and implementation science—are just a few of the many exciting areas of opportunity in cancer research.
Tackling the problem of cancer from many different angles will enable a future where:
- Understanding the Mechanisms of Cancer: Researchers have a comprehensive understanding of cancer biology that catalyzes the development of new ways to prevent, detect, diagnose, and treat cancer
- Preventing Cancer: More cancers are prevented because a person’s cancer risk will be known and reduced effectively
- Detecting and Diagnosing Cancer: Fewer people suffer and die from cancer because the disease and its precursors can be detected and diagnosed at the earliest possible stage
- Treating Cancer: All patients with cancer have safe and effective treatments
- Advancing Public Health in Cancer: All population groups benefit equally from advances in cancer research
This vision can only be achieved with robust and sustained support for cancer research, allowing investigators across the country to pursue their most innovative ideas in all areas of science. Long-term investments in cancer research will help all people live longer, healthier lives.
Understanding the Mechanisms of Cancer
Virtually all major advances against cancer originated with discoveries in the basic sciences. Basic research reveals new concepts about the causes of cancer and how it develops, progresses, and responds to therapy. This knowledge is essential for finding new ways to prevent, detect, and treat the disease.
NCI’s support of basic cancer research is critical. Long-term investments in research without immediate clinical application are not typically made by industry. One of the main ways NCI supports basic cancer research is through peer-reviewed research project grants, which fund most investigator-initiated science.
Virtually all major advances against cancer originated with discoveries in the basic sciences.
The return on NCI’s sustained investment in basic scientific research has been remarkable. For example, more than 40 years ago, scientists studying how retroviruses cause cancer discovered the first human oncogene (a gene that can transform a normal cell into a cancer cell). This novel and unexpected insight into cancer development, and other insights that followed, opened previously unexplored areas of cancer biology—ultimately leading to a new era of precision oncology and new approaches for cancer prevention, detection, and treatment.
Similarly, NCI-supported scientists investigating how immune responses are regulated applied their findings to unleash the power of the immune system to attack cancer, thus leading to many of the immunotherapies available today.
With the creativity of NCI-funded researchers and innovative new technologies, what new insights will be possible in the future? What additional, unsuspected causes of cancer might be discovered? What fundamental findings in cancer biology will lead to the next cancer treatment breakthrough? What new technology might be developed that revolutionizes cancer research?
The knowledge gained from our investments in basic research will drive tomorrow’s advances to help patients with cancer and individuals at risk of the disease.
To improve our understanding of the many diseases we call cancer, we must unravel the complexity of how normal cells become cancerous and how cancer cells grow, survive, and spread throughout the body. To do this, NCI is focused on the following goals:
1. Develop a Comprehensive Understanding of the Molecular and Cellular Basis of Cancer
A more complete understanding of cancer cell biology will enable new prevention, detection, and treatment approaches, which take advantage of vulnerabilities identified in cancer cells and their precursor lesions. Major objectives are to:
- Understand the genetic changes that give rise to cancer, as well as how genes are abnormally regulated (e.g., epigenetics)
- Identify how tumors evolve and respond to or resist treatment
- Study how cellular processes—such as cancer cell metabolism, stress responses, and cell-cycle regulation—contribute to cancer development and progression
2. Understand How Cancer Cells Interact with Normal Cells in the Body to Support or Suppress Tumor Development and Progression
Cancer can start in almost any tissue in the body, and the tissue in which a cancer arises and spreads can influence its molecular characteristics. This illustrates the importance of understanding the interactions between cancer cells and the surrounding normal cells to develop new prevention and treatment approaches. Major objectives are to:
- Characterize the components of the tumor microenvironment—including the cancer cells, connective tissue cells (fibroblasts), immune cells, bacterial cells (the tumor microbiome), blood vessels, and nerves—and determine their individual and collective influences on tumor progression and regression
- Understand the mechanisms by which cancer cells communicate with surrounding normal cells and enlist their help in promoting tumor growth
- Elucidate how cells and tissues in other parts of the body interact with cancer cells to prevent or promote metastasis (spread)
Prevention research, supported by NCI and others, has contributed to the decline in the overall rate of cancer incidence seen in the United States during the last 25 years.
NCI’s commitment to funding cancer prevention research is especially important because the private sector is hesitant to conduct such research due to the many economic, scientific, logistical, regulatory, and legal considerations that must be addressed.
NCI funding has supported major advances in cancer prevention, including the development of a hepatitis B virus vaccine to prevent liver cancer; demonstration that the drugs tamoxifen and raloxifene (Evista) can reduce the risk of breast cancer in women at increased risk of the disease; and the development of human papillomavirus (HPV) vaccines to prevent the majority of cervical, vaginal, vulvar, anal, rectal, oropharyngeal (throat), and penile cancers.
NCI funding has supported major advances in cancer prevention.
Major opportunities in cancer prevention are before us. For example, discoveries made in cancer biology, immunology, and vaccine science are using the power of the immune system to prevent cancers that are not caused by infectious agents, which represent the vast majority of new cancer cases.
In the future it will be possible to vaccinate individuals at high risk of certain cancers, such as those with inherited cancer predisposition syndromes, training their immune systems to protect them against cancer development.
Strong investments in cancer prevention research by NCI will mean a future with lower cancer incidence and morbidity. In other words, fewer people will have to face the physical, financial, social, and psychological harms of a cancer diagnosis and treatment.
Strong investments in cancer prevention research by NCI will mean a future with lower cancer incidence and morbidity.
Just as we are increasingly able to identify the best treatments for a person’s cancer based on the genetic abnormalities of their tumor, understanding a person’s genetic risk factors and environmental exposures over time should enable us to tailor personalized measures to prevent cancer. This future can be realized by supporting the following goals:
1. Identify and Characterize Risk Factors for Cancer
Opportunities exist to identify genetic and environmental risk factors for cancer, in addition to those already known, and to understand how genes and the environment interact to influence cancer risk. Major objectives are to:
- Characterize the biology of precancerous lesions and their progression to cancer, including molecular signatures, or “fingerprints,” of the DNA damage and repair processes the cancer cells and their precursors have experienced
- Develop more-precise individualized assessments of cancer risk, allowing people at increased risk to receive the most appropriate medical care to manage that risk
2. Develop and Test New Approaches for Cancer Prevention
NCI is committed to discovering new cancer prevention approaches, including strategies based on an increased understanding of biological and behavioral factors. Major objectives are to:
- Develop and test new strategies to further reduce the impact of modifiable risk factors for cancer, such as unhealthy lifestyle choices
- Support research to fully leverage the immune system to prevent cancer (immunoprevention), including cancers caused by infectious agents and those that are not
- Identify new chemical agents or repurpose existing agents to prevent cancer (chemoprevention)
Detecting and Diagnosing Cancer
Cancer detection and diagnosis involve identifying the presence of cancer in the body and assessing the extent of disease—whether it is the initial diagnosis of a cancer or the detection of a recurrence. For some cancers, this definition can be expanded to include identifying precancerous abnormalities that are likely to become cancer, providing an opportunity for early intervention and preventing cancer altogether.
NCI funding has contributed to many major advances in cancer detection and diagnosis. For example, in 1979, NCI-supported research established the effectiveness of screening mammography for detecting early-stage breast cancer. In addition, NCI-sponsored studies demonstrated the effectiveness of lung cancer screening with low-dose computed tomography in reducing lung cancer mortality in 2011 and led to the first Food and Drug Administration (FDA) approval of an HPV test for cervical screening in 2014.
NCI-funded research is fueling innovative new technologies that will change cancer detection and screening in the future. Someday, a simple blood draw (a liquid biopsy) in a doctor’s office may be used to detect, diagnose, and monitor many types of cancer. In addition, imaging technologies coupled with artificial intelligence may be able to identify the presence, type, stage, and major genetic features of a cancer without the need for an invasive biopsy.
Someday, a simple blood draw in a doctor’s office may be used to detect, diagnose, and monitor many types of cancers.
Additional research will enable the development of more-sensitive, accurate, and cost-effective methods of detecting, diagnosing, and, in some cases, preventing cancer in the future.
Advances in biomedical technologies are enabling the development of new tools for cancer detection and diagnosis. Our goals include the following:
1. Improve Current Methods and Develop New Methods of Detecting Cancer and Its Precursors
NCI’s investments in this area include: developing new or improved detection and diagnosis methods that are more accurate and of greater clinical utility than those available today, and optimizing the use of proven methods by physicians and health care systems. In addition, producing cost-effective technologies and tests that can be used in all resource settings is essential. Major objectives are to:
- Improve current cancer imaging technologies to enhance their ability to detect cancer or its precursors at the earliest possible stage
- Develop and test new technologies that will enable the identification of cancerous and precancerous cells at the molecular level and provide information about their biological activity
- Find novel ways to combine technologies to enhance cancer detection and diagnosis
- Develop and refine noninvasive tests for the early and accurate detection and diagnosis of cancer
2. Identify and Validate New Biomarkers that Can Be Used for the Early Detection and Diagnosis of Cancer and Its Precursors
The use of tumor biomarkers (e.g., measuring the presence of specific proteins or other molecules in tumor specimens) and imaging biomarkers (e.g., measuring the selective uptake of radioactive substances by tumors visualized through PET scans) is widespread in oncology. NCI’s objectives in developing additional biomarkers are to:
- Identify novel biomarkers, such as changes in cellular metabolites measured in exhaled breath
- Identify and validate new types of blood-based biomarkers, such cell-free DNA fragmentation patterns
- Identify new types of tissue-based biomarkers based on differences in the electrical or mechanical properties of cells or tissues
Thanks to NCI-funded research, patients with cancer have a greater number of more-effective and less-toxic therapeutic options today than ever before.
NCI’s support for treatment research extends from investigations of the fundamental mechanisms of cancer, the development of drugs that target those mechanisms, and testing new cancer therapies in clinical trials. NCI also supports critical research infrastructure, including the National Clinical Trials Network (NCTN), which provides robust support for NCI-sponsored diagnosis, treatment, and screening trials.
Patients with cancer have a greater number of more-effective and less-toxic therapeutic options today than ever before.
Breakthroughs in molecularly targeted therapies and immunotherapies have revolutionized the treatment landscape for patients. A better understanding of cancer biology has fueled the development of new classes of drugs, including the first small-molecule molecularly targeted therapy (imatinib [Gleevec]), the first immune checkpoint inhibitor (ipilimumab [Yervoy]), and the first genetically engineered cell-based immunotherapy (tisagenlecleucel [Kymriah]). In 2018 alone, FDA approved 19 new cancer treatments, and NCI-funded research contributed to the development and/or testing of most of them.
Breakthroughs in molecularly targeted therapies and immunotherapies have revolutionized the treatment landscape for patients.
Many more treatment innovations are on the horizon. For example, recent research is creating optimism that, one day, there may be targeted treatments for so-called “undruggable” cancer drivers. These include the oncoproteins RAS and MYC and tumor suppressors such as p53 and PTEN. While clinical testing is needed, the availability of these targeted treatments will be a hallmark of unprecedented progress for patients who have few therapeutic options.
Immense opportunities exist in cancer treatment. One day it will not only be possible to molecularly characterize a patient’s cancer cells, but the cellular composition of their tumor and even the composition of their microbiome will inform treatment decisions. With this information, doctors will select therapies, or combinations of therapies, for each patient—and avoid ones that will have unacceptable side effects. This future will only be possible through additional research investment.
Investing in the opportunities present in cancer research today will further improve the outlook for both adults and children with cancer. Fully realizing the potential to identify, study, and test new cancer therapies requires additional research to achieve the following goals:
1. Discover and Develop New Cancer Treatments, including Those that Involve Molecularly Targeted Therapies and Immunotherapies, as well as Treatment Combinations
Therapies that target the molecular changes in a person’s cancer and immunotherapies that unleash the power of the immune system against the disease are revolutionizing the potential impact of cancer care. Because these newer therapies provide durable clinical benefits to only a small proportion of patients, though, we must develop new therapeutic approaches. Our major objectives are to:
- Identify and characterize new targets for cancer treatment, such as abnormal proteins that are responsible for cancer cell survival, growth, and spread
- Develop new ways to leverage the rapid progress in cancer immunotherapy—including identifying predictive biomarkers, developing novel immune targets, and combining therapies—to benefit more patients
- Understand mechanisms of drug resistance, a major cause of treatment failure in patients, and develop strategies that target these mechanisms, including the use of combination therapies
- Identify and develop additional biomarkers to monitor treatment benefits and harms to aid clinicians in selecting the most appropriate treatments for patients
2. Improve Traditional Cancer Treatment Approaches, including Surgery, Radiation Therapy, and Chemotherapy
Surgery, radiation therapy, and chemotherapy remain important options for cancer treatment. NCI funds research to improve the effectiveness and utilization of these treatments. We must learn to use them more effectively and minimize their side effects. Our major objectives are to:
- Understand how to combine therapies, including different types of treatment (e.g., radiotherapy with immunotherapy)
- Tailor treatments to avoid overtreatment and unnecessary toxic effects (e.g., de-escalation studies)
- Advance the development of precision radiotherapy to target tumors more specifically and spare the surrounding normal tissue from radiation damage
- Support innovations in cancer surgery, including improving patient selection and approaches to minimize the impact on normal tissue
Advancing Public Health in Cancer
Studying cancer on a population-wide scale yields findings that are used to protect the health of people and their communities. These findings are also used to inform the development and implementation of policies and programs to reduce the burden of cancer. As part of this effort, NCI collaborates with other federal agencies and organizations at the local, state, national, and global levels to support and share evidence-based interventions for cancer control.
NCI-funded research has contributed to major improvements in public health and cancer control. For example, cervical cancer mortality declined 60% in the United States from 1975 through 2016. NCI-supported researchers contributed to technologies such as the Pap and HPV tests, elucidated the cancer-causing nature of HPV, and laid the foundation for the development of the HPV vaccines available today.
In addition, substantial progress has been made in reducing the prevalence of cigarette smoking and its resulting harms since the first Surgeon General’s Report on smoking and health was published over 50 years ago. In 1964, the prevalence of regular tobacco smoking among adults was 42%. By 2017, it had declined to 14%. Tobacco use is linked to at least 15 cancer types and ending smoking in the United States would eliminate almost one-third of the nation’s cancer deaths.
We are striving to prevent all HPV-associated cancers, eradicate the incidence of cancers caused by tobacco use, dramatically reduce cancer disparities, and see major improvements in the quality of life of cancer survivors in the future. Additional investments in cancer control, population health, and survivorship will continue to reduce cancer risk, incidence, and mortality and improve the lives of cancer survivors and the general population.
Cancer will continue to grow as a major public health issue in the United States as the population ages. More research and innovation are needed across the entire spectrum of cancer—from prevention to detection and diagnosis to treatment and survivorship—to successfully achieve the following goals:
1. Develop Public Health Interventions to Reduce the Risk of Cancer
It has been estimated that 30%–50% of cancers diagnosed today could be prevented by reducing exposure to tobacco smoke and other environmental carcinogens, maintaining a healthy body weight, and receiving recommended cancer screenings and vaccinations. Identifying innovative ways to help people change their behaviors and make healthy lifestyle choices will have dramatic impacts. Our major objectives are to:
- Further reduce tobacco use among all population groups and better understand the health effects of electronic nicotine delivery devices (e-cigarettes) and alternative tobacco delivery methods (e.g., snus and hookahs)
- Develop informational and behavioral interventions to reduce obesity and reduce the risk of obesity-associated cancers
- Study how physical activity influences cancer incidence and patient outcomes and translate the knowledge gained into effective interventions for individuals at risk, patients undergoing treatment, and survivors who have completed treatment
- Develop interventions to increase the use of proven, effective cancer prevention strategies (e.g., HPV vaccination) and screening methods (e.g., colorectal and lung cancer screening)
Identifying innovative ways to help people change their behaviors and make healthy lifestyle choices will have dramatic impacts.
2. Support Research to Reduce Cancer Disparities
Certain populations, including specific racial/ethnic groups and rural populations, suffer disproportionately from some cancers. The reasons for these disparities include both biological and nonbiological factors. A major nonbiological factor is inadequate access to cancer screening tests, preventive interventions, and high-quality cancer care. Our major objectives are to:
- Develop innovative, portable, low-cost technologies for cancer screening and diagnosis in a doctor’s office, a clinic, or other local care setting
- Develop smoking cessation interventions targeted to socioeconomically disadvantaged populations that could be made scalable for broad population impact
- Evaluate the effectiveness of a single-dose of HPV vaccines and of different formulations of these vaccines, including formulations that do not require refrigeration, to increase HPV vaccine uptake, especially among medically underserved populations
- Enhance participation of racial/ethnic minorities and the underserved in NCI-sponsored clinical trials
3. Ensure that Cancer Survivors Have the Highest Possible Quality of Life
Many cancer survivors suffer from health problems caused by the disease or its treatment that require additional and, perhaps, ongoing care. Survivors of childhood cancers, on average, will have to deal with these effects for much longer than adult survivors. Our major objectives are to:
- Understand the short- and long-term adverse effects of cancer and its treatment, and develop interventions to reduce their impact on patients
- Identify risk factors, including genetic factors, that contribute to differences between patients in the occurrence and intensity of adverse effects, including the risk of second or recurrent cancers
- Investigate what role, if any, comorbidities (other health problems) play on treatment-related adverse effects so we can more effectively care for the whole patient
- Develop interventions to promote healthy behaviors among cancer survivors to improve both health outcomes and quality of life