Biennial Report of the Director

Research in Diseases, Disorders, and Health Conditions

The Burdens of Cancer and the Necessity and Promise of NIH Research

Although significant progress has been made in reducing the burden of cancer in America, cancer remains a leading cause of death. According to the CDC, in 2010, cancer maintained its long-standing place as the second leading cause of death in the U.S., surpassed only by heart disease. In that same year, 573,855 people died of some form of cancer1 and an estimated 1,529,560 individuals were newly diagnosed with cancer.2 Also in 2010, according to studies by the NCI Surveillance Research Program,3 medical costs associated with cancer totaled $124.6 billion and are projected to reach at least $158 billion by 2020 (in 2010 dollars).4 Although U.S. death rates for the most common cancers and for all cancers combined have decreased significantly since 1995, the annual number of cancer diagnoses is projected to rise to 2.6 million because of the growth and aging of the population.

Cancer research funded and conducted by NIH is critical to the national, as well as global, effort to ameliorate and reduce the adverse effects of cancer on the health and lives of cancer patients, their families, and communities, and on the social and economic well-being of institutions, societies, and entire nations. Formidable challenges confront that effort. Cancer itself is not a single disease but is, rather, a complex of more than 100 diseases in which genetic changes disrupt cell function. Moreover, within each type of cancer an individual’s tumor can differ greatly due to complex biological factors. Cancer arises from alterations in the interactions among layered biological systems. The many different forms of cancer can be understood only by characterizing these systems and how they interact. NIH cancer research programs aim to improve our understanding of cancer as a multiscale, multidimensional disease system. This approach provides a context for research on: 1) identifying substances in our environment that we know or suspect will cause cancer; 2) preventing cancer through use of risk assessments based on genetic susceptibilities and environmental exposures; 3) detecting and diagnosing cancer based on knowledge of cancer signaling pathways and biomarkers; 4) predicting cancer progression and outcomes based on examination of the tumor microenvironment and interactions between tumor cells and surrounding, noncancerous cells; 5) developing targeted interventions for individual cancer patients based on the biology of their individual tumors and predictions of their response to treatment; and 6) addressing the unique needs of the growing number of cancer survivors.

Precision medicine based on molecular characterization of individual cancers is the vision that provides the foundation for NIH’s approach to cancer research and treatment. With the progressive realization of this vision, clinicians will have the ability to use detailed information about an individual’s cancer and employ molecular and clinical data to guide the selection of therapies that are most likely to be safe and effective for that person. Precision medicine promises to improve quality of life for cancer survivors by minimizing adverse side effects of therapy and reducing disparities among populations currently experiencing an excess burden of cancer.

1 Murphy SL, et al. Table B. Deaths and death rates for 2010 and age-adjusted death rates and percent changes in age-adjusted rates from 2009 to 2010 for the 15 leading causes of death in 2010: United States, final 2009 and preliminary 2010. National Vital Statistics Reports; 60(4):31. Available at: https://www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_04.pdf.
2Howlader N, et al. SEER Cancer Statistics Review 1975-2009 (Vintage 2009 Populations), National Cancer Institute. Bethesda, MD. Available at: https://seer.cancer.gov/csr/1975_2009_pops09/.
3 For more information, see https://surveillance.cancer.gov/.
4Cancer Prevalence and Cost of Care Projections, National Cancer Institute, Bethesda, MD. Available at: https://costprojections.cancer.gov/.

The Organization of Cancer Research at NIH

Although cancer research is conducted and supported by multiple ICs at NIH, NCI spearheads the Agency’s efforts and programs along the continuum from basic to clinical to translational research. Five NCI extramural divisions support research at 650 U.S. universities, hospitals, cancer centers, specialized networks and research consortia, and other sites as well as research in more than 20 other countries. NCI’s two intramural divisions—the Center for Cancer Research5 and the Division of Cancer Epidemiology and Genetics6—conduct basic, translational, clinical, and population research, aimed at fundamental discoveries related to cancer causes and mechanisms, genetics, and host immunological and other responses to cancer and aim to rapidly translate those findings into new preventive and detection methods and therapies. In addition, NCI also provides infrastructure to help the cancer research community, both in the U.S. and abroad, take advantage of the potential benefits of emerging technologies (e.g., genomics, proteomics, bioinformatics, and molecular imaging).

Cancer research conducted or supported by other NIH ICs is wide-ranging and often coordinated with NCI programs and grantees. Examples of cancer research within other ICs include:

5For more information, see https://ccr.cancer.gov/
6For more information, see https://dceg.cancer.gov/
7For more information, see https://www.nhlbi.nih.gov/whi/

NIH Funding for Cancer Research

NIH funding for cancer research was $5,823 million in FY 2010 and $5,488 million in FY 2011 for non-ARRA (regular appropriations) and $803 million in FY 2010 for ARRA appropriations.8

Summary of NIH Activities

Across NIH, cancer and cancer-related research activities are focused on two overarching goals: 1) prevent cancer at every opportunity and 2) ensure the best outcomes for those diagnosed with cancer. Specific objectives related to these goals include: understanding the causes and mechanisms of cancer; accelerating progress in cancer prevention; improving early detection and diagnosis; developing effective and efficient treatments; and building infrastructure for cancer research.
Cancer results from the complex interplay of genetic background and environmental factors. In some cases, a mutation of a single gene may be enough to increase cancer risk while in other cases, combinations of gene variants collectively contribute to an individual’s susceptibility to disease. A myriad of factors can influence cancer risk. In addition to carcinogens, such as those found in tobacco, and some infectious agents, physiological changes related to obesity or other factors can also play a role in initiating molecular aberrations in a cell’s genome.

Research that improves our understanding of these causes and mechanisms of cancer, from identifying novel risk factors to elucidating the processes of metastasis (the spread of cancer from the primary tumor site), is essential for the development and application of interventions to prevent cancer’s initiation and progression. NIH’s plan for deciphering the causes and mechanisms of cancer includes fundamental research into cell signaling that can provide important insights into the molecular regulators of cell growth and differentiation in a range of tissues. In addition, NIH supports studies in molecular epidemiology to define complex risk factors, research on the tumor macroenvironment and microenvironment, understanding the role of altered gene expression in cancer progression, and exploring the roles of susceptibility genes in cancer risk and initiation.

A primary challenge is dissecting the molecular basis of cancer. The Cancer Genome Atlas (TCGA),9 launched in 2006 as a collaboration between NCI’s Center for Cancer Genomics and NHGRI, is the largest, most comprehensive analysis of the molecular basis of cancer ever undertaken. The aim of TCGA is to identify and catalog all of the relevant genetic alterations in many types of cancer. The genomic information generated by TCGA could fuel rapid advances in cancer research and has already led to new therapeutic targets. It has suggested new ways to categorize tumors, which might allow clinical trials to focus on those patients who are most likely to respond to specific treatments. In addition, TCGA could also yield information critical to reducing health disparities associated with cancer. In conjunction with the NCI Center to Reduce Cancer Health Disparities,10 TCGA is working to ensure that adequate numbers of biospecimens are obtained from underserved and underrepresented populations to be included in TCGA analyses. Additionally, publicly available TCGA data are being analyzed by multiple research groups nationwide and include promising efforts to link medical imaging characteristics to genomic data to permit non-invasive characterization linked to the cancer genome.

8For funding of various Research, Condition, and Disease Categories (RCDC), please see https://report.nih.gov/categorical_spending.aspx.
9 For more information, see https://cancergenome.nih.gov/
10For more information, see https://crchd.cancer.gov/

A prime example of TCGA’s potential is illustrated by research targeting glioblastoma multiforme, an aggressive form of brain cancer. In the past year, glioblastoma multiforme investigators discovered that about 10 percent of patients with one of the four subtypes of glioblastoma multiforme are younger at diagnosis and live longer than patients with other subtypes of the disease, but their tumors are unresponsive to current intensive therapies. The molecular profile of this subtype offers new targets for developing drugs to treat this form of the disease more effectively. Research focused on ovarian cancer offers another illustrative example of the promise of fundamental insight offered by TCGA. Analysis of nearly 500 ovarian cancers through TCGA revealed several tumor subtypes, identified molecular pathways potentially important in tumor maintenance, revealed that mutations in the TP53 gene are found in virtually all of these cancers, and catalogued the large areas of the genome whose copy number is increased and decreased. The information gleaned from these as well as other rich sources of genomic data will inform a new generation of drug discovery and treatment options for addressing ovarian cancer and some 20 other cancer types currently under study at TCGA. The TCGA network has selected more than 6,000 gene and microRNA (miRNA) targets for sequencing that represent both protein-coding genes and gene encoding miRNAs.

Many other noteworthy NIH research initiatives are underway to illuminate the mechanisms of cancer. The Therapeutically Applicable Research to Generate Effective Treatments (TARGET)11 initiative seeks to identify and validate therapeutic targets for childhood cancers, such as acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma, osteosarcoma, and Wilms’ Tumor. TARGET investigators have identified mutations in a class of protein kinase genes called the Janus kinases that predict relapse in high-risk children with acute lymphoblastic leukemia. Protein kinase is an enzyme that modifies and functionally changes other proteins. TARGET utilizes high-throughput screening technology to identify the genetic abnormalities in these pediatric cancers, as does another initiative, the Cancer Genome Characterization Initiative.12 Investigators in the Clinical Proteomic Tumor Analysis Consortium13 are analyzing the sequences and quantities of proteins in samples collected through TCGA with the goal of comprehensive proteogenomic integration. Proteomics is biological research that combines proteomics (study of proteins) and genomics (study of genomes). Additionally, the Physical Sciences-Oncology Centers14 program supports innovative ideas that blend perspectives and principles of physical sciences and engineering with cancer biology and clinical oncology with the goal of enhancing the detection and treatment of cancer by increasing understanding of the physical and chemical forces that govern the emergence and behavior of cancer.

The Cancer Target Discovery and Development networ15 is accelerating the transition of molecular data to new treatments through gene validation studies as well as high-throughput screening of small molecules and research using mouse models. A number of other NCI resources also support studies in mouse models. The Mouse Models of Human Cancers Consortium16promotes the use of genetically engineered mice for mechanistic studies as well as to provide insight into new therapeutic strategies before they are tested in clinical trials. Collaborative Cross and Diversity Outbred Mice developed with NCI funding are being used to ascertain genetic determinants of therapeutic response and adverse events. Collaborative Cross mice that were developed in partnership with NIEHS, NIDA, and NCRR, are also being used for mouse GWAS to expose the gene, gene-gene, and gene-environment contributions to cancer susceptibility that are linked to lifestyle factors such as obesity, stress, diet, and lack of exercise.

11 For more information, see https://target.cancer.gov/.
12For more information, see https://cgap.nci.nih.gov/cgci.html.
13For more information, see https://proteomics.cancer.gov/programs/cptacnetwork.
14For more information, see https://physics.cancer.gov/centers/
15For more information, see https://ocg.cancer.gov/programs/ctdd.asp.

16 For more information, see https://www.nih.gov/science/models/mouse/resources/hcc.html.

NCI is conducting GWAS to identify genetic variants associated with cancer risk. The Cancer Genetic Markers of Susceptibility17 project, originally designed to identify common inherited genetic variations associated with risk for breast and prostate cancer, has grown into a robust research program involving GWAS for a number of cancers (i.e., pancreas, bladder, lung, kidney, brain, esophagus, stomach, testis, non-Hodgkin lymphoma, and osteogenic sarcoma). In addition, NCI’s longstanding investment in the follow-up of cancer-prone families has led to new efforts to discover rare gene variants using powerful new advances in whole-exome (the coding regions of the genome that are expressed into proteins) and whole-genome sequencing. To leverage these resources and ensure that the dramatic advances in genomics are incorporated into rigorous population-based studies, data from these initiatives are being made available to both intramural and extramural research scientists as well as those in the private sector through rapid posting to databases.18 Ultimately, findings from these studies may yield new preventive, diagnostic, and therapeutic interventions for cancer.

Studies through NCI’s Cohort Consortium,19a large-scale, international collaboration that includes over four million people, are evaluating the role of genetic susceptibility, environmental exposures (including nutrition), and gene-environment interactions for a range of different cancers. In addition, NCI has several ongoing and planned genome-wide association studies to identify genetic determinants of cancer risk, as well as the contributions of major determinants of health such as obesity and tobacco use. NCI has also funded a number of studies through its new Post-Genome Wide Association initiative, the goal of which is to translate GWAS findings into clinical and prevention applications by replicating findings, more accurately pinpointing genomic regions that cause cancer, unraveling the functions of genetic variants, and determining how environmental factors alter genetic risk.

Another major NIH initiative anchored to the goal of clarifying the environmental and genetic risk factors for cancer is the NIEHS-led Sister Study,20 which focuses on breast cancer. This study involves a cohort of 50,000 sisters of women who have been diagnosed with breast cancer. These unaffected sisters are being followed over time, with periodic health updates. The women who develop breast cancer during the follow-up period will be compared with those who remain healthy to identify factors associated with increased cancer risk.

17For more information, see https://cgf.nci.nih.gov/resources/cgems.html.
18For more information, see https://epi.grants.cancer.gov/dac/ and https://cgems.cancer.gov/data_access.html.
19For more information, see https://epi.grants.cancer.gov/Consortia/cohort.html.
20For more information, see https://www.niehs.nih.gov/research/atniehs/labs/epi/studies/sister/index.cfm.

NIH also is supporting a network of Breast Cancer and the Environment Research Programs (BCERPs)21 to study the impact beginning in the prenatal period through adulthood to determine which environmental exposures may predispose a woman to breast cancer. Initially established in 2003 through a collaboration involving NCI and NIEHS, BCERPs undertake multidisciplinary studies of the genetic, chemical, physical, and social factors that affect breast development during puberty and breast cancer predisposition. An epidemiologic study conducted as part of BCERP is prospectively following through puberty a multiethnic cohort of 7- and 8-year-old girls from the Kaiser Foundation Health Plan. Other researchers are studying a public school population of Caucasian and African American students, to determine how diet influences fat tissue and alter the effects of hormones on sexual maturation. The effects of endocrine disruptors (chemicals that interfere with the hormone system), irradiation, and psychosocial elements also will be studied. An important goal is to develop public health messages to educate young girls and women who are at high risk of breast cancer about the role of specific environmental stressors in breast cancer and how to reduce exposures to those stressors. Additionally, NIEHS had an ARRA contract to develop communication toolkits targeting parents and health care providers with key messages based on the BCERP research findings.

Other research into the causes and mechanisms of cancer has revealed that tumors function like organs, comprising many interdependent cell types that contribute to tumor development and progression. The relationship between tumors and their surrounding cellular environment evolves over time, strongly influencing tumor progression, metastatic potential, and responsiveness to treatment. The Tumor Microenvironment Network22is an NIH program focused on expanding our understanding of the role of the microenvironment in which a tumor originates and the critical role it plays during tumor development, progression, metastasis, and in conferring therapeutic resistance.

Furthermore, interest is growing in the scientific community about the relationship between inflammation and cancer. Inflammation is a response to tissue damage, whether resulting from physical injury, infection, exposure to toxins, or other types of trauma. NIH is pursuing research on the linkages between carcinogenesis and alterations in the microenvironment induced by inflammation. Current research on inflammation suggests that pro-inflammatory conditions contribute to the development of several types of cancer, including lung, stomach, and liver cancers, and may lead to new treatment approaches (for example, research efforts focused on inflammatory and fibrotic diseases of the esophagus, stomach, colon, pancreas, and liver—all of which are risk factors for the development of cancer in these organs). The Cancer and Inflammation Program23 constitutes a major component of NIH’s inflammation and cancer initiative, which partners expertise in inflammation and immunology with cutting-edge cancer etiology and carcinogenesis research.

Systems biology and systems genetics also are promising new fields of study that will increase our understanding of the causes and mechanisms of cancer. These disciplines focus on biological and genetic networks that can be measured, modeled, and manipulated rather than focusing on the individual components. Because this research requires multidisciplinary teams of experts in biology, medicine, engineering, mathematics, and computer science, NIH launched the Integrative Cancer Biology Program (ICBP)24to develop a framework for these activities. The ICBP has funded twelve integrative biology centers around the U.S. to provide the nucleus for the design and validation of computational and mathematical models of cancer. Networks of genes can be found and their associations with cancer tested and quantified, and parallel association studies can be conducted in relevant human populations.

21 For more information, see https://www.niehs.nih.gov/research/supported/centers/breast-cancer/index.cfm.
22For more information, see https://tmen.nci.nih.gov/.
23For more information, see https://ccr.cancer.gov/labs/lab.asp?labid=790.
24 For more information, see https://icbp.nci.nih.gov/.

NIH is expanding its research portfolio related to the basic biology of tumor stem cells (also referred to as tumor-initiating cells). Tumor stem cells may be responsible for the recurrence of malignancy in some cancers. These cells often are resistant to standard chemotherapeutic agents but may contain unique target molecules that allow their eradication with novel molecular therapeutics. Progress has been made in identifying tumor stem cells in multiple myeloma, acute myeloid leukemia, and breast cancer.
Basic research is unlocking our understanding of what happens in the cellular microenvironment in and around a developing tumor. One aspect of that research is finding ways to boost the body’s own immune responses to cancer that offers a new array of cancer treatments. The molecule CTLA-4, for example, inhibits the actions of T cells, part of the body’s self-defense against tumors. Research on antibodies that block CTLA-4’s action and allow the body to ramp up its own T-cell attacks on tumors led to the recent approval of the drug ipilimumab for melanoma, and clinical trials using ipilimumab and other anti-CTLA-4 antibodies are underway for some lung and prostate cancers.

Numerous other NCI projects and initiatives are investigating the roles of infectious agents and the immune system in cancer. Current evidence indicates that as many as one in five cancers may have an infectious cause; this number is larger in low and middle-income countries. When infectious causes are discovered, the agent can represent a molecular target for intervention or a biomarker for screening (e.g., human papillomavirus infection of the cervix, hepatitis B and C viruses infection of the liver). NCI-funded investigators are working with U.S. and foreign scientists to study the role of immune dysfunction in the formation of tumors , in part through the study of cancer in HIV-infected individuals, and also by investigating the contributions of chronic inflammation to cancer development. NCI is also actively investigating therapies that utilize host immune cells and responses to combat tumor growth and metastasis. For example, the Center for Excellence in Immunology,25 an intramural research program, fosters the discovery, development, and delivery of novel immunologic approaches for the prevention and treatment of cancer and cancer-associated viral diseases. The complex interactions between tumors and surrounding cells that influence cancer progression are being characterized by projects funded through ICBP and the Tumor Microenvironment Network. Projects funded through the recent Advanced In vivo Imaging to Understand Cancer Systems initiative are focused on integrating advanced in vivo imaging technologies with systems biology approaches to understand complex cancer phenomena at highest resolution.

NCI supports research to explore the effects of obesity and energy balance on cancer risk as well as to inform the development of improved methods for assessing energy intake, fat distribution, sedentary behavior, and physical activity. NCI also evaluates mechanisms by which obesity may be related to carcinogenesis using high-throughput technologies such as multiplex assays (an assay that measures multiple analytes in a single cycle), along with other analytic approaches. An example of an initiative in this area is the Transdisciplinary Research on Energetics and Cancer 26 Program, which was developed to foster collaboration among scientists and accelerate progress toward reducing cancer incidence, morbidity, and mortality associated with obesity, low levels of physical activity, and poor diet.

For reasons that are self-evident, the optimal strategy for individuals, their caregivers, and society at large is to prevent cancer. To this end, NIH research has multiple aims, including modifying behaviors that increase risk, mitigating the influence of genetic and environmental risk factors, and interrupting cancer process through early medical intervention.

One role of the trans-HHS National Toxicology Program, led by NIEHS, is to review the cumulative state of the science on the potential carcinogenicity of publicly registered substances such as chemicals (e.g. solvents and industrial salts), food additives and herbal medicines (e.g. saccharin, gingko Biloba), and other environmental agents (e.g. asbestos). Determinations are made as to whether a substance is a known human carcinogen or reasonably anticipated to be a carcinogen, as well as other potential toxicities. The findings of these investigations are published in the publically available document, Report on Carcinogens.27

Dramatic developments in technology and an enhanced, continually evolving understanding of the causes and mechanisms of cancer are proving crucial to the development of prevention strategies. Research across multiple disciplines will provide a more complete understanding of the interplay of molecular, behavioral, genetic, and other factors that contribute to cancer susceptibility. Identifying critical molecular pathways in precancerous lesions will provide new drug targets for preempting cancer. For example, the recent characterization of ovarian tumors through TCGA may inform development of a much needed screening assay for this disease, which is currently often detected in late stages. Genomic studies may also identify targets for chemoprevention.

The Consortia for Early Phase Prevention Trials28involve six major cancer research centers that lead multiple collaborative networks to assess the cancer prevention potential of new agents, with a focus on Phase I and II clinical trials. In addition to designing and conducting trials and recruiting participants, the Consortia work to 1) characterize the effects of potential agents on molecular targets, 2) identify biological events associated with cancer development, and 3) correlate these effects with clinical endpoints. Continued emphasis will be placed on identifying molecular drug targets, developing successful prevention strategies, and bringing these findings into clinical practice.

A major step forward in our efforts to prevent cancer has been the development of vaccines that target human papillomavirus (HPV). Persistent infection with HPV is recognized as the major cause of cervical cancer. Gardasil®, a FDA-approved vaccine against HPV types 6, 11, 16, and 18 (the viral types that cause approximately 70 percent of cervical cancers and 90 percent of genital warts) now is available. Other similar vaccines against HPV types 16 and 18, as well as vaccines that address additional subtypes, are in development. These vaccines have the potential to save thousands of women’s lives annually in the U.S. and several hundred thousand more each year worldwide. All of these vaccines resulted directly from epidemiological, basic, and preclinical research discoveries, as well as the development of a prototype HPV vaccine, by NIH scientists.

25For more information, see https://ccrod.cancer.gov/confluence/display/COEI/Home.
26For more information, see https://cancercontrol.cancer.gov/trec/.
27For more information, see https://ntp.niehs.nih.gov/?objectid=03C9AF75-E1BF-FF40-DBA9EC0928DF8B15.
28For more information, see https://prevention.cancer.gov/clinicaltrials/management/consortia.

In an effort to reduce the cancer incidence, morbidity, and mortality associated with obesity, low physical activity, and poor diet, NIH has funded the Transdisciplinary Research on Energetics and Cancer Research Centers, which foster collaboration among transdisciplinary teams of scientists. The Centers are studying factors that lead to obesity and the mechanisms by which obesity increases the risk of cancer. The initiative is connecting with a number of established initiatives in the areas of diet, physical activity, and weight and is integrated with the Strategic Plan for NIH Obesity Research.29

The knowledge that environment and behavior can play critical roles in the development of cancer has been fundamental to one of the greatest public health success stories of the 20th century: the reduction in tobacco use and related diseases. By the mid-1950s, the mysterious and alarming epidemic in lung cancer, a disease that was almost nonexistent in 1900, was linked to smoking behavior. In the last decade, overall cancer death rates have dropped for the first time in a century, driven largely by the dramatic reduction in male smoking from 47 percent in the 1960s to less than 23 percent today. About 40 percent of this drop in overall cancer rates has been credited to the dramatic reduction in male smoking and male lung cancer deaths since 1991 (more than 146,000 fewer deaths during 1991 to 2003 alone). This success has been due to public-private partnerships, and also is a trans-HHS victory, as significant research investments have been made over the last 50 years by NCI, NIEHS, NHLBI, NIDA, NIAAA, CDC, and AHRQ. In addition, untold numbers of cancer-related illnesses and deaths have been prevented through the decrease in exposure of non-smokers to environmental tobacco smoke due to recognition of these effects and widespread campaigns to limit or ban smoking in public places. Without these investments, 40 million Americans might still be smoking today, hundreds of thousands of them and those exposed with them would have died prematurely of a tobacco-related disease, and billions of dollars would have been spent on their treatment.

Multiple NIH Institutes have co-funded seven Transdisciplinary Tobacco Use Research Centers,30 which seek to identify familial, early childhood, and lifetime psychosocial pathways associated with smoking initiation, use, cessation, and patterns of dependence. Research on the genetics of addiction, physiological biomarkers, and advanced imaging techniques should allow the development of individualized and community approaches to the prevention and treatment of tobacco-related diseases. The Transdisciplinary Tobacco Use Research Center model demonstrates the feasibility and benefits of scientific collaboration across disciplines and public-private partnerships. With a special focus on cessation, the NCI-sponsored State and Community Tobacco Control Policy and Media Research initiative will investigate the effectiveness of state and community tobacco control policy and media interventions. Focus areas include secondhand smoke policies, tax and pricing policies, tobacco industry marketing and promotion, mass media countermeasures, and community and social norms.

29Strategic Plan for NIH Obesity Research – A Report of the NIH Obesity Research Task Force (2011). Available at: https://www.obesityresearch.nih.gov/About/StrategicPlanforNIH_Obesity_Research_Full-Report_2011.pdf.
30For more information, see https://dccps.nci.nih.gov/tcrb/tturc/.

The NIH-supported Community Clinical Oncology Program (CCOP)31 provides a network for greater participation in clinical trials on cancer prevention and treatment. There are 48 CCOPs and 16 Minority Based-CCOPs32 (CCOPs with 30 percent of their new patients from minority populations) currently funded in 35 states and Puerto Rico. The program involves 3,645 physicians participating in 415 hospitals, working on more than 70 active prevention and control trials. The groups responsible for developing and implementing cancer prevention and control clinical trials are known as Research Bases; 13 Cooperative Groups and Cancer Centers have grants to serve as CCOP Research Bases.

The HMO Cancer Research Network (CRN)33conducts cancer prevention, early detection, treatment, long-term care, and surveillance research, using data systems of 14 HMOs nationwide. Studies of lifestyle change include research into energy balance (integrated effects of diet, physical activity, and genetics on growth and body weight) as a way to control cancer incidence. The SEER Program34, which has collected data since 1973, regularly samples approximately 26 percent of the U.S. population and has obtained information on 5.7 million cancer cases—380,000 cases are added each year. This database provides critical data on cancer trends and is maintained in collaboration with the CDC’s National Center for Health Statistics, the Census Bureau, and the North American Association of Central Cancer Registries.

The National Outreach Network 35 is a multidisciplinary program that bridges NCI-supported outreach and community education efforts with cancer health disparities research and training programs. Working through community health educators, the National Outreach Network disseminates cancer information and approaches tailored to racial/ethnic communities for cancer prevention and control and also works to enhance recruitment and retention in cancer research.

Detecting and diagnosing tumors early in the disease process, before the tumor becomes invasive and metastatic, can dramatically improve a patient’s odds for successful treatment and survival, and prevent a large proportion of cancer deaths. Therefore, NIH seeks to accelerate the translation of basic research findings into sophisticated, minimally invasive procedures that harness imaging, genomic, proteomic, nanotechnology, and other advanced early-detection and diagnostic techniques.

Molecular profiling is an ongoing effort at NIH, from work at the bench to larger initiatives. In the area of molecular diagnostics, NIH has formed the Early Detection Research Network (EDRN)36to bring a collaborative approach to the discovery, development, and validation of early-detection biomarkers for clinical application. Another NIH program, Strategic Partnering to Evaluate Cancer Signatures,37 focuses on confirming, evaluating, and refining “signatures” derived from the molecular analysis of tumors (i.e., biomarkers detection) to improve patient management and outcomes. In addition, the Cancer Genome Anatomy Project38focuses on determining the gene expression profiles of normal, precancerous, and cancerous cells to improve detection, diagnosis, and treatment. The Cancer Genome Anatomy Project Web site makes tools for genomic analysis available to researchers worldwide.

31For more information, see https://dcp.cancer.gov/programs-resources/programs/ccop.
32For more information, see https://ncccp.cancer.gov/Related/MBCCOP.htm.
33For more information, see https://crn.cancer.gov/about/.
34For more information, see https://seer.cancer.gov/.
35For more information, see https://crchd.cancer.gov/inp/non-overview.html.
36For more information, see https://edrn.nci.nih.gov/.
37For more information, see https://www.cancerdiagnosis.nci.nih.gov/scientificPrograms/specs.htm.
38For more information, see https://cgap.nci.nih.gov/.

Yet another area of research that holds promise for advancing molecular diagnostics is proteomics—the study of complex arrays of proteins produced by cells and tissues. Since its completion nearly a decade ago, the Human Genome Project has catalyzed progress in proteomics research, and NIH has taken a leading role in facilitating the translation of proteomics from laboratory research to clinical application through the Clinical Proteomic Technologies for Cancer initiative. The overall objective of this initiative is to build the foundation of technologies (assessment, optimization, and development), data, reagents and reference materials, computational analysis tools, and infrastructure needed to systematically advance our understanding of protein biology in cancer and accelerate basic science research and the development of clinical applications. The Clinical Proteomic Technologies for Cancer comprises three integrated programs: the Clinical Proteomic Technology Assessment for Cancer network, the Advanced Platforms and Computational Sciences program, and the Proteomic Reagents and Resources Core.

Screening for cancers within the large population of people who do not have obvious cancer symptoms represents a major undertaking for health care providers in the U.S. Most medical organizations, including the United States Prevention Services Task Force, recommend screening for breast, colon, and cervical cancers based on demonstrated mortality reductions in randomized trials (breast and colon cancers) and large population cohort studies (cervical cancer). There is evidence that the process of finding these cancers among the many screened is not optimal. Whereas performance characteristics of individual screening tests (sensitivity, specificity, positive predictive value) are relatively well known, analogous performance characteristics of the entire process remain understudied. To pursue the long-term objective of optimizing the screening processes in community practice, NIH is supporting Population-based Research Optimizing Screening through Personalized Regimens Research Centers.39 This multi-site, coordinated, transdisciplinary initiative has the scientific goal of supporting research to better understand how to improve the screening process (recruitment, screening, diagnosis, referral for treatment) for breast, colon, and cervical cancer.

As previously noted, efforts at NIH, and at NCI and NIDA in particular, to study and reduce the use of tobacco products have contributed to a sustained annual reduction in age-adjusted cancer mortality rates over the past decade and more, not just among men, where we have seen steady declines, but now also among women. Current and former heavy smokers still remain at high risk of developing lethal lung cancers, which are the leading cause of cancer mortality. The recently concluded National Lung Screening Trial40 provided the first clear demonstration that a screening procedure among this high risk population can be effective in reducing mortality from lung cancer. Current and former heavy smokers who were screened with low-dose helical computed tomography were 20 percent less likely to die of lung cancer than were peers who received standard chest x-rays. This promising finding combined with proven tobacco prevention and cessation efforts could save many lives among those at greatest risk. The U.S. Preventive Services Task Force has commissioned modeling studies of lung cancer screening by investigators in NCI’s Cancer Intervention and Surveillance Modeling Network to fully assess the risks and benefits of screening with low-dose helical computed tomography. In the coming years, NCI seeks to support a wide range of prevention and detection efforts that could have equally significant outcomes, including enhanced screening for breast, colorectal, and cervical cancers; new imaging approaches for more accurate and earlier detection of glioblastoma multiforme, breast, and renal cell carcinoma; and identification of biomarkers as early warning signs of the presence of or likelihood of developing many kinds of cancers. NCI research will continue to develop an enhanced understanding and ability to modify behaviors that increase the risk of developing cancer, reduce exposure to environmental carcinogens, and mitigate the effects of environmental or genetic cancer risks.

Developing more effective, more efficient, and less toxic cancer treatments is at the heart of the NIH cancer research agenda. A better understanding of the fundamental mechanisms leading to cancer development, progression, and metastasis is improving the identification of key biochemical pathways in the disease process as targets for treatment. Acceleration of target validation and the development of new treatment modalities are being made possible by recent advances in biomedical science and technology. A rapid translation from development to delivery will ensure that promising treatments move safely and efficiently from preclinical investigation through late-stage clinical trials and into clinical practice.

NIH is working on multiple fronts in the drive to develop new, more effective therapies for cancer. One innovative initiative, the NCI Experimental Therapeutics Program (NExT),41 combines the extensive expertise of cancer treatment and diagnosis in anticancer drug development with the dynamic NIH intramural research resources. Drug discovery and development projects that enter the NExT pipeline are focused on unmet needs in cancer therapeutics that are not adequately addressed by the private sector. NExT is designed to advance clinical practice and bring improved therapies to cancer patients. The discovery engine of this program is the Chemical Biology Consortium.42 The NCI has established this collaborative network comprising 12 of the top Specialized and Comprehensive Screening and Chemistry Centers with world-class capabilities covering high-throughput methods, bioinformatics, medicinal chemistry, and structural biology. Additionally, the highly successful Developmental Therapeutic Program provides the resources needed to facilitate discovery and late-stage preclinical development through the final steps of development to first-in-human studies. Concurrent molecular imaging and/or pharmacodynamic assay development provided by the Cancer Imaging Program,43National Clinical Target Validation Laboratory,44 and CCR allow early assessment of potential clinical biomarkers. These coordinated and focused R&D processes enable continued incorporation of new data and disease insights into every step of the discovery and development process, thereby increasing the potential for successful clinical evaluation of agents. The new Clinical Assay Development Program45 has been established to accelerate the movement of promising clinical laboratory assays from the research setting into clinical trials. The program provides access to tissue and laboratory resources for the analytical and clinical validation of assays to predict response to cancer treatment or disease outcome. Services are provided to efficiently develop diagnostic tests that address clinical needs, including co-development of targeted agents and predictive markers. In support of the NExT initiative, the Center for Advanced Preclinical Research46will accelerate development of therapeutics and diagnostics for human diseases by providing state-of-the-art animal models for preclinical studies that are genetically programmed to develop diseases in the same way they arise in humans.

39 For more information, see https://appliedresearch.cancer.gov/networks/prospr/
40 For more information, see https://www.cancer.gov/clinicaltrials/noteworthy-trials/nlst.
41 For more information, see https://next.cancer.gov/.
42 For more information, see https://next.cancer.gov/discoveryResources/cbc.htm.
43 For more information, see https://next.cancer.gov/pdResources/imaging.htm.
44 For more information, see https://next.cancer.gov/pdResources/pharmacodynamics.htm.
45 For more information, see https://cadp.cancer.gov/.
46 For more information, see https://atp.ncifcrf.gov/atpi/ppt/capr

Another program, the Cancer and Inflammation Program,47 supports cancer-related basic, translational, and clinical research in imaging sciences. Program initiatives include the development and delivery of image-dependent interventions for malignant and premalignant conditions; standardized models for the design of clinical trials that use imaging technologies; development of emerging imaging technologies, including nanotechnology, proteomics, and high-throughput screening; and development of imaging methods for cancer detection and treatment and for monitoring responses to therapy.

NCI investments in basic research lead to identification of potential therapeutic targets, many of which are validated and pursued by commercial interests. With the NExT initiative and other similar programs, NCI seeks to complement rather than compete with the private sector and often takes the lead on high-risk projects or those focused on rare cancers. Drugs against targets that have been characterized in part by NCI-funded researchers are already being used to treat cancer and/or are being tested in clinical trials. For example, Phase III clinical trials have been recently initiated to test therapies targeting the genes BRAF in melanoma and ALK in lung cancer. NCI supports a large portfolio of translational and preclinical studies that are focused on identifying, validating, and testing strategies for the treatment of cancer. The Comparative Oncology Pr48ogram provides an integrated mechanism through which the study of naturally occurring cancers in animals can generate new information about cancer and help translate biological concepts into clinical application. As part of this effort, and to evaluate novel therapeutic strategies for cancer, the Comparative Oncology Program has established a multicenter collaborative network of extramural comparative oncology programs to design and implement preclinical trials involving domesticated animals.

Using genomics to match drugs to the patients most likely to benefit from them, and conversely sparing patients courses of treatment from which they will not benefit, promises to be among the new modalities for successfully managing cancer. The potential therapeutic impact of basic discoveries made by TCGA and other efforts in cancer genomics has been dramatically illustrated within the past year by the development of effective drugs against metastatic melanoma. In 2003, studies of cancer genomes uncovered a common mutation in BRAF, a gene that encodes a protein known as B-raf. Early stage clinical trials at NCI-designated Cancer Centers of drugs targeted against the mutant BRAF enzyme showed that most melanomas with the relevant mutation regressed dramatically.49 Although tumor regression generally lasted less than a year, NCI-supported investigators have already pinpointed the cause of resistance to BRAF inhibitors, outlining a pathway to more sustained control of this lethal disease.50 A Phase III clinical trial is currently underway targeting ALK mutations in lung cancer.51 Such targeted treatments, made possible by deeper understanding of the genetic and molecular workings of cancer cells, can only be pursued with robust and sustained support both for fundamental research and for faster integration of research into clinical applications to improve patient outcomes.

47For more information, see https://imaging.cancer.gov/
48For more information, see https://ccrod.cancer.gov/confluence/display/CCRCOPWeb/Home
49For more information, see https://www.cancer.gov/ncicancerbulletin/061411/page2
50For more information, see https://www.cancer.gov/ncicancerbulletin/112911/page2
51For more information, see https://www.cancer.gov/ncicancerbulletin/090611/page2.

The emerging scientific landscape of precision medicine made possible by genomic information about cancer offers the promise of significant advances for current and future cancer patients. This effort is complemented at NCI by a new initiative to engage investigators with novel ideas. A funding opportunity announcement (Request for Applications) was released in the fall of 2011 soliciting research applications to address NCI’s 24 Provocative Questions52—important but non-obvious questions that will stimulate NCI’s research communities to use laboratory, clinical, and population sciences in especially effective and imaginative ways. The potentially game-changing answers to these scientific questions could influence the directions taken by NCI-sponsored research in the future, and could contribute to an even greater wave of discovery and progress against cancer.

The Repository of Molecular Brain Neoplasia Data (REMBRANDT)53is an online portal that integrates genomic data from several hundred brain tumors with clinical information about how patients responded to treatments, allowing researchers to dissect relationships between genomic traits and outcomes as well as conduct in silico investigations of potential therapeutic targets. The Trial Assigning Individualized Options for Treatment, or TAILORx,54is examining the possibility that a molecular profiling test that examines many genes simultaneously can help predict whether women with early-stage breast cancer would benefit from chemotherapy in addition to radiation and hormonal therapy. Incorporation of molecular data into clinical decision making could spare some women unnecessary treatment if chemotherapy is not likely to impart substantial benefit. The new Provocative Questions initiative may facilitate identification of molecular targets and markers for testing in future clinical trials by promoting research to identify the genetic and epigenetic changes that are most critical to the maintenance of oncogenesis as well as the properties of nonmalignant lesions that predict the likelihood of progression to invasive or metastatic disease.

In order to facilitate the translation of molecular therapeutic approaches to clinical use in the context of radiotherapy, the Radiation Research Program55tests NCI-developed drugs for their efficacy as radiosensitizers under a variety of in vitro environmental conditions and carries out in vivo radiation response studies. The program also fills an essential role by coordinating the transfer of NCI-developed drugs to extramural and foreign investigators interested in radiation studies, while avoiding duplication of effort between research groups. Efforts are underway to rescue chemotherapeutic drugs abandoned due to systemic toxicity and to formulate efficient platforms for gene specific short-interfering RNA (siRNA) delivery using nanotechnology-based constructs.

Innovative research in genetics, imaging, and cancer molecular signatures is laying the groundwork for customized cancer patient care. The Advanced Technology Program56 accelerates the delivery of new treatments to patients by developing and applying advanced technologies—such as biomedical imaging. The NCI imaging facility for clinical cancer research will fuse imaging and pathology in the evaluation of patients throughout treatment. The NIH Center for Interventional Oncology57 offers new and expanded opportunities to investigate cancer therapies using imaging technology to diagnose and treat localized cancers in a targeted and minimally or noninvasive manner. This interdisciplinary environment combines training, patient treatment, and translational research and development in interventional oncology. Researchers funded through the Quantitative Imaging Network58 are developing and validating quantitative imaging methods and software tools for the measurement of response to drug or radiation therapy for use in clinical trials.

52For more information, see https://provocativequestions.nci.nih.gov/.
53For more information, see https://caintegrator.nci.nih.gov/rembrandt/.
54For more information, see https://www.cancer.gov/clinicaltrials/noteworthy-trials/tailorx.
55For more information, see https://rrp.cancer.gov/.
56For more information, see https://atp.ncifcrf.gov/.
57For more information, see https://www.cc.nih.gov/centerio/index.html.
58 For more information, see https://wiki.nci.nih.gov/display/CIP/QIN.

Clinical trials are a critical step in moving potential therapies into clinical practice. NCI supports clinical trials through a number of mechanisms, including the Cooperative Group Program, which is designed to promote and support clinical trials of new cancer treatments, explore methods of cancer prevention and early detection, and study quality-of-life and rehabilitation issues.59The Cooperative Groups are now being reorganized to streamline the development and execution of trials, to select and prioritize trials through stringent peer review, and to fully fund the most promising and innovative studies. In an effort to maximize molecular characterization of cancers, biological specimens from trial participants will be collected for future research. Other trials are conducted within the intramural research program and with extramural support of investigator-initiated projects. NCI has also implemented the Biomarker, Imaging, and Quality of Life Studies Funding Program,60which supports promising correlative studies related to biomarkers, imaging, and patient quality of life, in association with Phase III and large Phase II trials. In order to facilitate management and coordination of the clinical trials portfolio, NCI is creating the Clinical Trials Reporting Program,61 a comprehensive database that will contain regularly updated information on all interventional trials.

NCI also encourages both intramural and extramural collaborations as part of its effort to develop new treatments for cancer. One example involves the drug rapamycin, which specifically and potently acts upon an essential signaling pathway in head and neck squamous cell carcinoma, the most common of the head and neck cancers. As part of an international initiative headed by NIDCR, scientists collected hundreds of head and neck cancer tissues from all over the world.62Examinations of the collected tissues confirmed that the mammalian target of rapamycin is a good target for treating head and neck cancer. Such findings led scientists to develop novel mouse models to test the impact of rapamycin administration on head and neck cancer, which was remarkable. Rapamycin caused the regression of established cancer lesions and prevented the development of new ones from pre-malignant lesions. New evidence in animal models suggests that rapamycin may also halt the spread of head and neck cancer to other parts of the body. In collaboration with NCI, NIDCR investigators have begun a clinical trial to evaluate the possible survival benefits of treating head and neck cancer patients with rapamycin before surgical removal of their tumors. These studies may lead to improvement in the overall five-year survival rate for head and neck cancer, which has remained constant at 50 percent for more than three decades. Melding basic science breakthroughs with decades of existing clinical data on rapamycin administration, this clinical trial could clear the way for more targeted and effective treatment of head and neck cancer patients.

59For more information, see https://www.cancer.gov/cancertopics/factsheet/NCI/clinical-trials-cooperative-group.
60For more information, see https://biqsfp.cancer.gov/.
61For more information, see https://www.cancer.gov/clinicaltrials/conducting/ncictrp/main.
62Molinolo AA, et al. Clin Cancer Res. 2007;13(17):4964-73. PMID: 17785546.

Research on the quality of cancer care is essential to ensure the best outcomes for all who may be affected by cancer. Research in this area includes surveillance as well as epidemiological and cost-effectiveness studies. In addition, quality-of-life research increases our understanding of the impact of cancer on patients, survivors, and their family members—many of whom are themselves at increased risk for cancer due to shared cancer-causing genes, lifestyles, or environmental exposures. Dissemination of research helps ensure that the knowledge gained through NIH-supported research is appropriately and effectively communicated to health care providers, policymakers, and the public.

The Cancer Intervention and Surveillance Modeling Network63 is a consortium of NCI-sponsored investigators that seeks to improve our understanding of the impact of cancer control interventions (e.g., prevention, screening, and treatment) on population trends in incidence and mortality using statistical modeling. The network is focused on meeting the expanding scientific need for tools which assist in synthesizing emerging evidence in a timely manner due to the extraordinary pace of developments in cancer control technologies, basic science studies investigating molecular and biological determinants of cancer risk, upcoming results from clinical trials, and new health-related data.

NIH focuses on cancer treatment as a primary area for quality-of-care research and the translation of research findings into practice. To this end, several collaborative projects have been initiated:

Thanks in large part to the success of new treatment strategies, the population of cancer patients surviving more than five years from diagnosis continues to grow. NIH supports research and education efforts aimed at professionals who care for cancer patients and survivors. The Office of Cancer Survivorship69addresses the physical, psychosocial, and economic impacts of cancer diagnosis and its treatment and the need for interventions to promote positive outcomes in survivors and their families. Important early findings suggest long latencies for treatment-related effects and highlight the need for extended follow up, early identification, and intervention before complications become more serious.

63For more information, see https://cisnet.cancer.gov/
64For more information, see https://outcomes.cancer.gov/networks/qccc/.
65For more information, see https://outcomes.cancer.gov/areas/assessment/comwg.html.
66 For more information, see https://outcomes.cancer.gov/cancors/.
67For more information, see https://healthservices.cancer.gov/surveys/poc/.
68For more information, see https://ncccp.cancer.gov/.
69For more information, see https://dccps.nci.nih.gov/ocs/office-survivorship.html.

To improve the outcomes of cancer patients, advances in knowledge must be effectively disseminated to the public and health care providers. The Cancer Control P.L.A.N.E.T.70 internet-based portal is a collaborative effort aimed at providing access to data and resources that can help cancer control planners, health educators, program staff, and researchers to design, implement, and evaluate evidence-based cancer control programs. P.L.A.N.E.T. assists local programs with resources that help them determine cancer risk and burden within their state and helps states identify potential partners. P.L.A.N.E.T. also provides online resources for interpreting research findings and recommendations and accessing products and guidelines for planning and evaluation.

Due in part to an explosion of information through any number of communication channels, including health information in the news media where cancer consistently ranks first among disease-specific news coverage, the public may at times hear conflicting or confusing information regarding cancer prevention recommendations and other health information. Health communication is a rapidly evolving field. To monitor changes and trends in health and cancer communication, NCI developed the Health Information National Trends Survey,71which is a national survey uniquely dedicated to learning how people find, use, and understand health information. Survey researchers examine how different communication channels are used by adults 18 years and older, including the Internet, to obtain vital health information for themselves and their loved ones. Program planners use the data to address barriers to effective health information usage across populations, and create more effective communication strategies. Finally, social scientists use the data to study health communication in the information age in order to recommend strategies for reducing the burden of cancer throughout the population.

NCI has made significant progress in expanding access to clinical trials for patients in community settings and for minority and underserved populations. Representing 340 hospitals and 2,900 physicians, the CCOPs enroll one-third of all participants in NCI cancer prevention, control and treatment trials nationwide. The current 16 Minority-Based CCOPs, comprising 55 hospitals and 475 physicians, and including 100 minority investigators, enroll patients into approved trials in areas with at least 30 percent underserved or minority populations. Minority-Based CCOPs have an average of 64 percent minority participants on trials at their sites. The NCI Community Cancer Center Programs was expanded from the original 16 pilot sites to a total of 30 sites with the goal of improving the quality of cancer care for more than 50,000 new cancer patients from rural, inner-city, and underserved communities each year and providing them the opportunity to participate in cancer research

NCI also invests in research to elucidate the factors that contribute to cancer health disparities. The Basic Research in Cancer Health Disparities initiative supports research to understand the biological mechanisms for cancer disparities among various racial and ethnic populations. The program investigates genetic/biological differences and cellular mechanisms that may lead to cancer disparities among various populations. The Centers for Population Health and Health Disparities72 program supports transdisciplinary research involving social, behavioral, biological, and genetic studies to elucidate the causes of health disparities and devise effective methods of preventing, diagnosing, and treating disease and promoting health. Using a regional approach, the Geographical Management of Cancer Health Disparities Program73is working to support biospecimen collection, development of bioinformatics platforms, clinical trials recruitment and retention, emerging technologies applications, and the development of research projects that focus on health disparities in racial/ethnic minority and underserved communities. As part of a broader Center to Reduce Cancer Health Disparities Biospecimen Awareness/Education and Collection Campaign, the Geographical Management of Cancer Health Disparities Program is also working to raise awareness about the importance of biospecimens and to educate minority populations about biospecimen research. Working in collaboration with TCGA, this national campaign aims to increase the collection of high-quality breast and prostate cancer specimens from racial/ethnic minority and underserved populations, as well as raise awareness and education about biospecimen research.

The incidence of cancer in low and middle income countries is projected to increase in the coming years. It is estimated that approximately 70 percent of cancer deaths will occur in low and middle income countries. High prevalence of cancer risk factors such as smoking, unhealthy diet, and infections are attributable to this increase, as are improvements in infectious disease management, health care delivery, and sanitation, which have augmented population longevity. The NCI Center for Global Health74 was launched in 2011 to support NCI’s goal to advance cancer research, build expertise, and leverage resources across nations. The Center focuses on reducing the global burden of cancer by supporting research programs and activities in cancer prevention, screening and early detection, diagnosis, treatment, palliation, and survivorship. The Center builds capacity for cancer research in the United States and other countries through training and education as well as research cooperation with other countries. The Center has offices in other countries, including India, China, and Belgium, and has established research networks in Latin America, the Caribbean, and Ireland.

The infrastructure required for initiating and sustaining a robust, multi-front effort to advance the science and treatment of cancer is exceptionally complex and varied in terms of its components. One such component is technology; NIH places a high priority on technology development to support both research and the application of research findings to improve health care delivery, emphasizing the areas of bioinformatics, cancer imaging, proteomics, and nanotechnology. As NIH-supported scientists begin to apply new discoveries to cancer prevention, early detection, and treatment, it will be important to integrate the tools and insights of research, science, and technology as effectively as possible.

The Cancer Biomedical Informatics Grid® (caBIG®)75is an important initiative designed to accelerate research discoveries and improve patient outcomes by supporting the sharing of data and tools among researchers, physicians, and patients throughout the cancer community. caBIG® has developed and freely distributed more than 40 software tools with applications in basic and clinical research on cancer and other diseases. NIH is committed to extending caBIG® across the broader cancer research and care community. More than 1,500 individuals, representing more than 450 organizations in 13 countries, have so far participated in caBIG® projects. caBIG® technologies have been used to link the 66 Cancer Centers, NCI Community Cancer Centers Program, TCGA, other NIH Institutes, FDA, and international partners.

The new BIG Health Consortium™ is a public-private partnership among key stakeholders in health care including patient advocates, health care providers, payers, product innovators, investors, and information technologists. Its mission is to show how and why personalized medicine works. Through a series of demonstration projects, BIG Health™ will model a new approach in which clinical care, clinical research, and scientific discovery are linked. The key enabler for this linkage is the informatics infrastructure that NIH has already developed—caBIG®.

The Alliance for Nanotechnology in Cancer, a comprehensive endeavor involving both public and private sectors, is designed to accelerate the application of nanotechnology to cancer research. This initiative supports research on novel nanodevices to detect and pinpoint the location of cancer at its earliest stages, deliver anticancer drugs specifically to malignant cells, and determine in real time whether these drugs are effective in killing those cells. Programs of the Alliance include the Nanotechnology Characterization Laboratory; Cancer Nanotechnology Platform Partnerships; Centers of Cancer Nanotechnology Excellence; Innovative Technologies for Molecular Analysis of Cancer; and Tumor Stem Cells in Cancer Biology, Prevention, and Therapy.

Given the global burden of cancer and opportunities to identify new approaches in prevention and treatment through international collaborative research, NIH is strengthening health research infrastructure and building global research capacity through the International Tobacco and Health Research and Capacity Building Program. This program promotes transdisciplinary approaches to reduce the global burden of tobacco-related illness and is designed to promote international cooperation between U.S. investigators and scientists in low- and middle-income nations where tobacco consumption is a current or anticipated public health problem. Because the overwhelming majority of smokers begin tobacco use before they reach adulthood, the program emphasizes research on determinants of youth smoking in diverse cultural and economic settings, as well as effective ways to prevent young people from starting to smoke.

A cornerstone of the infrastructure for NIH-sponsored cancer research is the NCI’s Cancer Centers Program, which focuses on transdisciplinary approaches to basic, population, and clinical research. Centers with comprehensive designation must have robust portfolios in each of these areas and must also demonstrate professional public education and outreach activities in the communities they serve. Specialized Programs of Research Excellence (SPORE) grants, each of which focuses on a specific organ site, such as breast or lung cancer, or a group of highly related cancers, such as gastrointestinal cancers, involve both basic and clinical/applied scientists (team science) and support projects that will result in new approaches to prevent, detect, diagnose, and treat human cancers.

The 66 NCI-designated Cancer Centers conduct some of the highest quality basic, translational, and population research to improve cancer prevention, diagnosis, and treatment while also stimulating innovative pilot projects in new investigational areas.
NCI-designated cancer centers are increasingly reaching out to community oncology practices and minority and underserved patient populations. They are also committed to delivering high-quality care. A program has been established to pre-qualify and re-qualify annually all of the comprehensive cancer centers to perform advanced imaging so that both quality of the imaging and shortened time to clinical trial initiation can be assured.

The SPOREs foster bi-directional translational research by supporting multi-project, interdisciplinary, and in some cases, multi-institutional research that will result in diverse new approaches to the prevention, early detection, diagnosis and treatment of human cancers. SPOREs create an environment for inter-SPORE collaboration and collaboration with other government and non-governmental groups to increase cross-fertilization of ideas, leverage resources, to reduce duplication and to ensure access of resources to scientific community ultimately facilitating the movement of SPORE research along the translational science continuum. SPOREs encourage involvement of patient advocates and support preclinical and early-stage clinical studies focused on molecular pathways associated with organ-site specific cancers, with emphasis on therapeutic targets. New treatments are developed concomitantly with predictive markers that identify patients most likely to respond to specific treatments. Promising therapies are advanced to NCI Cooperative Groups or industrial partners for evaluation in later stage clinical trials. SPOREs also support novel projects focused on the identification of cellular and molecular markers to improve early cancer detection, diagnosis, and risk assessment to reduce cancer incidence, morbidity and mortality, to extend survival, and to increase the quality of life of cancer patients.

Research workforce development is critical to maintaining and enhancing the nationwide (as well as global) infrastructure for cancer research. NCI, in particular, is committed to cultivating and supporting a cadre of researchers that span the career continuum; gaps at any stage of this continuum will compromise the quality of cancer research. NCI is investing in early-stage investigators to attract talent and ensure the future of cancer research and is also supporting established investigators who have proven their ability to conduct robust science and who provide mentoring for the next generation of researchers. NCI supports training within the intramural research program and through training awards to institutions and individuals in the extramural community. NIH will continue to invest in attracting the best and brightest graduate students and postdoctoral fellows—including those from populations underrepresented in biomedical research—for example, through the Ruth L. Kirschstein National Research Service Award (NRSA) training program. NCI-awarded NRSAs support the training and mentoring of predoctoral and M.D./Ph.D. or other dual-degree students in laboratory and/or clinical research, helping them to become productive, independent research investigators and clinician-scientists.

NCI also supports training in a number of other disciplines. The Physical Science-Oncology Centers program trains undergraduate, graduate, and postdoctoral trainees with the aim of cultivating a workforce capable of working at the interface of the physical sciences and cancer biology. Additionally, the Basic Behavioral and Social Science Opportunity Network (OppNet) offers educational activities and short-term career development experience to encourage new and established investigators to engage in basic behavioral and social science research. The Interagency Oncology Taskforce, a partnership with FDA, is designed to train scientists in cancer-related scientific research and research-related regulatory review, policies, and regulations. Finally, NCI also offers support to investigators interested in translational and clinical research. The SPORE Career Development Programs support investigators who wish to develop or refocus their careers on translational cancer research in specific organ-site malignancies. The Cancer Clinical Investigator Team Leadership awards provide two years of funding to exceptional mid-level clinical investigators who lead NCI-sponsored clinical trials but are not principal investigators at NCI-designated Cancer Centers.

70For more information, see https://cancercontrolplanet.cancer.gov/.
71 For more information, see https://hints.cancer.gov/
72For more information, see https://cancercontrol.cancer.gov/populationhealthcenters/cphhd/index.html.
73For more information, see https://crchd.cancer.gov/inp/gmap-overview.html.
74 For more information, see https://www.cancer.gov/aboutnci/globalhealth.
75 For more information, see https://cabig.nci.nih.gov/.

Conclusion—Realizing the Vision of Precision Medicine

Through both extramural and intramural initiative, NIH is progressively realizing its vision of precision medicine and care for all those who are affected by cancer. With sustained, robust public support, NIH will continue to make critical advances in the effort to reduce the morbidity and mortality associated with the second leading cause of death among American adults.