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Cancer Treatment Research

Credit: National Cancer Institute

Why Cancer Treatment Research Is Critical to Progress against the Disease

Research on the treatment of cancer is fundamental to improving outcomes for patients affected by the disease. These efforts include the development of more effective and less toxic treatments, such as targeted therapies, immunotherapies, and cancer vaccines, as well as the improvement of therapies that have existed for decades, such as chemotherapy, radiation therapy, and surgery. And some studies address better management of a treatment’s toxic effects, thereby improving a patient’s ability to receive effective cancer treatment. Still other studies test whether less intensive therapy or no therapy at all will result in the same outcome.

Opportunities in Cancer Treatment Research

Decades of research on the biology of cancer have revealed insights into the mechanisms that drive the disease. Data from molecular and other studies indicate that, even within a given cancer, there are differences in how the cancer behaves and how it responds to treatment. In addition to identifying genetic, epigenetic, and other molecular changes that may promote the development and growth of tumors, researchers have learned about the ways that tumors can survive and thrive in the body.

For example, tumors have the ability to develop their own blood supplies, manipulate the immune system to tamp down immune responses, and recruit normal cells to help them grow. Just as important, tumor cells can ignore signals that normally tell old or damaged cells to die.

This new understanding has created opportunities to develop targeted therapies—cancer treatments that target the specific changes, most often in proteins, that underlie the growth and development of cancer. Surgery, radiation therapy, and standard chemotherapy will continue to play an important role in treating cancer, but the emergence in recent years of targeted therapies and of immunotherapies, which harness the power of the immune system to fight cancer, have expanded the treatment options available to patients with certain types of cancer.

Another important opportunity comes from the finding that similar molecular changes are shared among cancers that arise at different sites in the body. For example, The Cancer Genome Atlas (TCGA) Research Network recently identified genomic similarities between endometrial and other types of cancer, including breast, ovarian, and colorectal cancers. Therefore, treatments that target specific molecular changes may work not only against the cancer for which they were developed, but also against tumors from other sites that happen to carry the same alterations.

Challenges in Cancer Treatment Research

Although many advances in cancer treatment have been made in recent decades, numerous challenges remain before the goal of providing the best possible outcome for all patients diagnosed with cancer can be achieved.

For example, developing targeted therapies requires the identification of good molecular targets—that is, targets that play a key role in cancer cell growth and survival—and the design and development of drugs that effectively "hit", or bind to, those targets. However, some potential targets that have been identified appear to lack places to which an anticancer drug can bind and, therefore, have been called "undruggable." Finding ways to design drugs that effectively hit these targets is a major challenge.

Drug resistance—either to traditional chemotherapy drugs or to newer targeted therapies—is another challenge in cancer treatment. More research is needed to uncover the mechanisms of drug resistance and identify ways to overcome it.

The genomic characterization of tumors has provided both new opportunities for cancer treatment and new challenges. The discovery that each individual’s cancer has a unique constellation of gene mutations and other alterations increases the complexity of identifying treatments that are likely to work best for a given person’s cancer. However, even within a single patient, different parts of a single tumor, or different metastatic tumor nodules in the same patient, may not be identical in terms of the molecular changes that are present. This raises the possibility that a drug might be effective in one part of a person’s tumor but not in another.

Moreover, although recent advances in immunotherapy have been dramatic, this approach to treating cancer is still in its infancy. Many challenges remain, including how to optimize the immune response to eradicate cancer while avoiding runaway responses that cause autoimmune damage to normal tissues. An additional challenge is determining why current immunotherapies work in some patients but not in others.

Many challenges also remain in optimizing cancer treatment with conventional chemotherapy drugs, radiation therapy, and surgery. Research on the identification and development of additional chemotherapeutic agents is needed, as is research to refine the delivery of lethal doses of radiation therapy to tumors while sparing the surrounding normal tissues from harm. Another challenge is the development of ever more effective treatments to alleviate the side effects of all forms of cancer therapy.

NCI's Role in Cancer Treatment Research


For more than 50 years, NCI has played an active role in the cancer drug development process from conducting preclinical studies in the laboratory to testing potential therapies in humans. NCI’s influence is reflected in the fact that approximately half of the chemotherapeutic drugs currently used by oncologists to treat cancer were discovered and/or developed by NCI-funded researchers.

The institute sponsors treatment clinical trials that are conducted by NCI researchers at the National Institutes of Health in Bethesda, MD, and at cancer centers, hospitals, and community practices around the country. The Cancer Therapy Evaluation Program (CTEP) in NCI’s Division of Cancer Treatment and Diagnosis (DCTD) functions as the institute’s primary clinical evaluator of new anticancer agents, radiation treatments, and surgical methods. For details, see NCI’s Clinical Trials Programs and Initiatives.

NCI is also leading efforts on several fronts to determine the most efficient and effective ways to evaluate new anticancer therapies, such as developing new clinical trial designs that are more appropriate for precision medicine and immunotherapies.

Drug Discovery and Development

NCI’s Developmental Therapeutics Program (DTP), which is also part of DCTD, has a repository of more than 400,000 compounds that have gone through some kind of screening process. About 80,000 compounds have been screened since 1990. DTP participates in all stages of preclinical drug discovery and development.

A compound is first screened against a variety of human tumor cell lines, growing in tissue culture dishes, to test its ability to prevent the growth of specific kinds of cancer cells. If the drug shows some evidence of anticancer activity, extensive testing in animals will determine whether it is effective enough for testing in humans.

NCI’s Center for Advanced Preclinical Research (CAPR), a component of NCI’s Center for Cancer Research (CCR), conducts comprehensive preclinical testing of early-stage candidate drugs. Candidate compounds are assessed for antitumor efficacy and selectivity in genetically engineered animal models. Other projects at CAPR include the development of imaging technologies to monitor disease and treatment.

Of all the compounds screened by NCI, about 40 percent come from industry, and the rest primarily come from academic collaborators. Another source of novel compounds is the Natural Products Branch, a part of the DCTD DTP that collaborates with agencies throughout the world to collect thousands of plant and marine organisms to screen for potential anticancer compounds.

To expedite drug discovery, NCI provides sample sets of more than 140,000 synthetic chemicals, 80,000 natural products extracted from plants and marine organisms, and other biological materials to investigators who might have discovered potential cancer-associated molecular targets.

NCI's Biopharmaceutical Development Program develops, manufactures, and provides novel biological agents for early-phase clinical trials that industry and other labs are not prepared to develop. For example, the BDP developed and produced the monoclonal antibody ch14.18 for the treatment of high-risk neuroblastoma before it was subsequently commercialized.

The NCI Formulary, a public–private partnership between NCI and pharmaceutical and biotechnology companies, gives investigators at NCI-Designated Cancer Centers quicker access to approved and investigational agents for use in cancer clinical trials. Eligible investigators may apply for access to agents from the available formulary list and test them in new preclinical or clinical studies, including combination studies of formulary agents from different companies.

Academic and private industry laboratories engaged in drug discovery may face financial and technical burdens that keep promising therapeutic agents from reaching patients. NCI has helped and will continue to help the academic and private sectors overcome various therapeutic development barriers, in particular by supporting high-risk projects and the development of therapies for rare cancers.

NCI has created the Drug Resistance and Sensitivity Network (DRSN) to understand and counteract drug resistance in tumors and to exploit the sensitivity of cancer cells to specific treatments. The findings and models from this multidisciplinary network will inform the design of new clinical cancer treatments that can prevent or overcome drug resistance. The network is also building a collection of resources that can be used by cancer researchers examining mechanisms of drug resistance.


The Molecular Profiling to Predict Response to Treatment Program (MP2PRT) supports the characterization of biospecimens collected in NCI-sponsored clinical trials, including trials that are part of NCI's National Clinical Trials Network (NCTN) and the NCI Community Oncology Research Program (NCORP). By analyzing tumors from patients who were treated in completed clinical trials with published outcome results, the MP2PRT may lead to the development of predictive models that show which patients will benefit from different cancer therapies.

The NCTN Biospecimen Banks include a large collection of well-annotated biospecimens from patients enrolled in NCTN trials. NCI encourages the scientific community to use these biospecimens, regardless of whether the researcher is a member of an NCTN Group. Some NCTN biospecimen inventories can be found via NCTN Navigator, a resource for researchers seeking specimens to validate their analyses.

Human Tumor Cell Lines and Models

A unique resource in DTP’s anticancer drug discovery program is a collection of 60 human tumor cell lines that can be used to evaluate compounds for anticancer activity. The NCI-60 Human Tumor Cell Lines Screen represents nine different types of cancer: breast, ovary, prostate, colon, lung, kidney, brain, leukemia, and melanoma. These are the most frequently studied human tumor cell lines in cancer research, molecular pharmacology, and drug discovery.

The In Vitro Cell Line Screening Project (IVCLSP) supports the DTP anticancer drug discovery program. This project is designed to screen up to 3,000 compounds per year for potential anticancer activity using the NCI-60 human tumor cell lines. The aim is to prioritize, for further evaluation, promising synthetic compounds or natural product samples with anticancer properties.

NCI has developed the Patient-Derived Models Repository to serve as a resource for public–private partnerships and for academic drug discovery efforts. The patient-derived models (PDMs) being developed for the repository are derived from tumor tissue or circulating tumor cells (CTCs) and are propagated both in vitro using 2D or 3D cell culture systems and in vivo passaging in mice as patient-derived xenografts (PDXs). These PDMs are early-passage, molecularly characterized, and clinically annotated and will be made available to the research community at a minimal cost. All associated metadata will be available for review through the publicly accessible website without the need to acquire a model beforehand.

PDXs have limitations. Because they are often developed in isolation, it can be difficult to validate and replicate results from trials using these models. Also, collections of PDX models are often too small to reflect the diversity of patient tumors found in large-scale clinical trials. To improve PDXs, NCI has created the collaborative Patient-Derived Xenografts Development Network (PDXNet). The network consists of PDX Development and Trial Centers (PDTCs) and Minority-PDX Development and Trial Centers (M-PDTCs), which develop models, including racially and ethnically diverse PDX models, on a large scale. The network aims to improve standardization procedures, to design model validation methods to advance the translation of PDX findings into clinical cancer treatments, and to advance the understanding of disparities among racially and ethnically diverse populations.

The international Human Cancer Models Initiative is generating novel human tumor-derived culture models with the goal of creating cancer models that recapitulate patients’ tumors as faithfully as possible. The models are annotated with genomic and clinical data and are available to the wider research community to define cancer pathways, determine mechanisms of drug resistance, and assess responses to small molecules. NCI contributes to the initiative by providing funding and support to two Cancer Model Development Centers.

Radiation Therapy, Cancer Vaccines, and Immunotherapies

Finding new ways to more specifically target radiation therapy to tumors and spare as much normal tissue as possible is paramount for maintaining patients’ quality of life and improving cure rates. NCI’s Radiation Research Program (RRP), which is part of DCTD, provides expertise to investigators who perform radiotherapy research and assists in establishing future radiation research directions.

Cancer treatment vaccines are designed to boost the body’s natural ability to protect itself, through the immune system, from dangers posed by damaged or abnormal cells, such as cancer cells. Researchers are developing treatment vaccines against many types of cancer and testing them in clinical trials.

Developing effective cancer treatment vaccines requires a detailed understanding of how immune system cells and cancer cells interact. CCR's Vaccine Branch studies basic mechanisms of immune response and molecular virology. These findings are applied to the development of vaccines and immunotherapy for the prevention and treatment of cancer and AIDS, as well as viruses that cause cancer.

Immunotherapies are treatments that stimulate the activities of specific components of the immune system or counteract signals produced by cancer cells that suppress immune responses. CCR researchers conducted pioneering research that has led to the first effective immunotherapies for selected patients with advanced cancer. These studies of cell transfer immunotherapy have resulted in durable complete remissions in patients with metastatic melanoma.

Learn about the wide range of research NCI supports to advance the field of cancer immunotherapy in NCI’s Role in Immunotherapy Research.

Translational Research

DCTD's Translational Research Program (TRP) supports efforts through the Specialized Programs of Excellence (SPOREs) to translate novel scientific discoveries from the laboratory to the clinic for testing in humans and to determine the biological basis for observations made in cancer patients or in populations at risk for cancer. Recent projects have included a study to define the importance of immunity to an antigen in melanoma therapy and targeted therapies for childhood acute lymphoblastic leukemia.

CCR's Developmental Therapeutics Branch (DTB) integrates both basic science and translational clinical programs. The basic science program focuses on cancer-specific genomic and epigenomic alterations, oxidative signaling, molecular pharmacology, and drug resistance. The translational clinical program focuses on novel therapeutic agents across a spectrum of diseases and disease mechanisms.

Within DTB, the Genomics and Bioinformatics Group explores the relationships between genomic alterations in malignant cells and their response to chemotherapeutic agents using molecular databases at the DNA, RNA, and protein levels.

The PREVENT Cancer Preclinical Drug Development Program helps bring new cancer preventing interventions and biomarkers through the early stages of research required before testing in human clinical trials. The program, which is part of NCI’s Division of Cancer Prevention, currently supports the development of a number of new agents and several drugs already in use for other diseases and conditions, including aspirin and the diabetes drug metformin. Clinical evaluation of these and other promising new agents and strategies to prevent cancer is performed by the Phase 0/I/II Cancer Prevention Clinical Trials Program.

Exceptional Responders Initiative and NExT

Exceptional responders are patients who respond to treatments that are not effective for most other patients. NCI launched the Exceptional Responders Initiative to determine whether certain molecular features of the malignant tissue in patients who respond exceptionally well can predict the responses of future patients to the same or similar drugs. In the study, investigators will study the molecular characteristics of tumors from patients who had an exceptional response to a systemic cancer therapy. Where possible, non-tumor specimens (or "normal" tissue) from the patients will also be examined, as these help in determining which mutations are present only in the tumor, rather than in normal cells and tissue.

NCI's Experimental Therapeutics Program (NExT) focuses on advancing breakthrough discoveries in basic and clinical research into new therapies to treat cancer patients. This translational research effort unites the drug development expertise of DCTD with CCR’s dynamic research programs and the facilities at the NIH Clinical Center to advance new therapeutic interventions from both the private and public sectors.

Supportive and Palliative Care

Supportive and palliative care studies focus on the prevention and treatment of acute and chronic symptoms and side effects related to cancer and its treatment. Research is also done to study the effect of treatment on cancer patients' quality of life and the psychosocial issues and strategies for care at the end of life. The NCI Community Oncology Research Program (NCORP) network supports studies on the molecular determinants of treatment toxicities and cancer-related symptoms, and on the management of treatment-related effects like fatigue, musculoskeletal pain, nerve damage, and ovarian failure.

As part of the Cancer Moonshot℠, NCI has created a network of multidisciplinary teams to collect, analyze, and interpret adverse event data and patient-reported outcomes (PRO) in cancer clinical trials. PRO data, such as health-related quality-of-life data, will help researchers, clinicians, and patients understand the side effects of cancer treatments and the degree to which patients tolerate these treatments.

NCI has established a collaborative research consortium, called Improving the Management of Symptoms during and following Cancer Treatment (IMPACT), to determine the best approaches for symptom management in cancer care delivery. Research centers within this consortium are testing integrated symptom monitoring and management systems in the clinic and analyzing the effects of those systems on patient outcomes, cancer treatment delivery, and health care utilization using randomized designs.