National Cancer Institute

The National Cancer Institute (NCI) is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S. National Cancer Program and conducts and supports research, training, health information dissemination, and other activities related to the causes, prevention, diagnosis, and treatment of cancer; the supportive care of cancer patients and their families; and cancer survivorship.

On June 10, 2017, President Donald J. Trump announced his intent to appoint Norman Sharpless as director of the National Cancer Institute.

NCI is the oldest and has the largest budget and research program of the 27 institutes and centers of the NIH. It fulfills the majority of its mission via an extramural program that provides grants for cancer research. Additionally, the National Cancer Institute has intramural research programs in Bethesda, Maryland and at the Frederick National Laboratory for Cancer Research at Fort Detrick, in Frederick, Maryland. The NCI receives more than $5 billion in funding each year.

The NCI supports a nationwide network of 69 NCI-designated Cancer Centers with a dedicated focus on cancer research and treatment and maintains the National Clinical Trials Network.

Timeline

 * 1937 - Creation of the NCI by the National Cancer Act of 1937
 * 1940 - First issue of the Journal of the National Cancer Institute published
 * 1944 - Congress made the NCI an operating division of the National Institutes of Health by the Public Health Service Act. Congress amended the Public Health Service Act with the National Cancer Act of 1971 to broaden the scope and responsibilities of the NCI "in order more effectively to carry out the national effort against cancer."
 * 1955 - NCI established the Clinical Trials Cooperative Group Program which included several research networks that conduct cancer clinical research primarily under the sponsorship of NCI.
 * 1957 - The first cancer (choriocarcinoma) was cured with chemotherapy at NCI.
 * 1960 - NCI began funding government-supported cancer centers
 * 1971 - President Nixon converted the Army's former biological warfare facilities at Fort Detrick, Maryland, to house research activities on the causes, treatment, and prevention of cancer.
 * 1971 - National Cancer Act of 1971 declares "war on cancer", establishes the National Cancer Advisory Board, and allots additional funding for cancer research
 * 1975 - The Frederick National Laboratory for Cancer Research opened in Frederick, MD as a Federally Funded Research and Development Center
 * 1993 -The NIH Revitalization Act of 1993 encourages NCI to expand efforts in prostate cancer, breast cancer, and other women's cancers and authorized increased appropriations.
 * 2009 - The American Recovery and Reinvestment Act of 2009 provided $10 billion in additional funding for the NIH; the NCI received $1.3 billion in funds.
 * 2016 - The 21st Century Cures Act increased funding for biomedical research. The "Cancer Moonshot" program promised additional support for cancer research.

Anti-cancer drug investigations
The NCI played an early role in the discovery of anti-cancer drugs in the U.S. According to a 1996 NCI analysis of drugs approved by the Food and Drug Administration (FDA), two-thirds of the anti-cancer drugs approved as of the end of 1995 were NCI-sponsored Investigational New Drugs: Alkylating agents
 * Chlorambucil (Leukeran) (1957)
 * Cyclophosphamide (Cytoxan) (1959)
 * Thiotepa (1959)
 * Melphalan (Alkeran) (1959) (IV in 1993)
 * Streptozotocin (Zanosar) (1982)
 * Ifosfamide (Ifex) (1988)

Antimetabolites
 * Mercaptopurine (1953)
 * Methotrexate (1953)
 * Thioguanine (1966)
 * Cytosine arabinoside (Ara-C) (1969)
 * Floxuridine (FUDR) (1970)
 * Fludarabine phosphate (1991)
 * Pentostatin (1991)
 * Chlorodeoxyadenosine (1992)

Plant alkaloids and antibiotics Synthetic drugs
 * Vincristine (Oncovin) (1963)
 * Actinomycin D (Cosmegen) (1964)
 * Mithramycin (Mithracin) (1970)
 * Bleomycin (Blenoxane) (1973)
 * Doxorubicin (Adriamycin) (1974)
 * Mitomycin C (Mutamycin) (1974)
 * L-Asparaginase (Elspar) (1978)
 * Daunomycin (Cerubidine) (1979)
 * VP-16-213 (Etoposide) (1983)
 * VM-26 (Teniposide) (1992)
 * Taxol (Paclitaxel) (1992)
 * Hydroxyurea (Hydrea) (1967)
 * Procarbazine (Matulane) (1969)
 * O, P'-DDD (Lysodren, Mitotane) (1970)
 * Dacarbazine (DTIC) (1975)
 * CCNU (Lomustine) (1976)
 * BCNU (Carmustine) (1977)
 * Cis-diamminedichloroplatinum (Cisplatin) (1978)
 * Mitoxantrone (Novantrone) (1988)
 * Carboplatin (Paraplatin) (1989)
 * Levamisole (Ergamisol) (1990)
 * Hexamethylmelamine (Hexalen) (1990)
 * All-trans retinoid acid (Vesanoid) (1995)
 * Porfimer sodium (Photofrin) (1995)

Hormones and steroids
 * DES (1950)
 * Prednisone (1953)
 * Fluoxymesterone (Halotestin) (1958)
 * Dromostanolone (Drolban) (1961)
 * Testolactone (Teslac) (1970)
 * Methyl prednisolone
 * Prednisolone
 * Zoladex (1989)

Biologicals
 * Alpha interferon (Intron A, Roferon-A) (1986)
 * BCG (TheraCys, TICE) (1990)
 * G-CSF (1991)
 * GM-CSF (1991)
 * Interleukin 2 (Proleukin) (1992)

Organization
The NCI is divided into several divisions and centers.

Intramural

 * Center for Cancer Research
 * The CCR includes approximately 250 internal NCI research groups in Frederick and Bethesda.


 * Division of Cancer Epidemiology and Genetics
 * DCEG is divided into the Epidemiology and Biostatistics Program and the Human Genetics Program.

Extramural

 * Division of Cancer Biology
 * DCB oversees approximately 2000 grants per year in the areas of cancer cell biology; cancer immunology, hematology, and etiology; DNA and chromosome aberrations; structural biology and molecular applications; tumor biology and microenvironment; and tumor metastasis. "Special Research Programs" falling under the aegis of the DCB include: Physical Sciences-Oncology Network, Cancer Systems Biology Consortium, Oncology Models Forum, Barrett's Esophagus Translational Research Network, New Approaches to Synthetic Lethality for Mutant KRAS-Dependent Cancers, Molecular and Cellular Characterization of Screen-Detected Lesions, Fusion Oncoproteins in Childhood Cancers, and Cancer Tissue Engineering Collaborative.


 * Division of Cancer Control and Population Sciences
 * Division of Cancer Prevention
 * Division of Cancer Treatment and Diagnosis
 * DCTD supports eight research programs: The Biometric Research Program, The Cancer Diagnosis Program, The Cancer Imaging Program, The Cancer Therapy Evaluation Program, The Developmental Therapeutics Program, The Radiation Research Program, The Translational Research Program, and The Office of Cancer Complementary and Alternative Medicine.


 * Division of Extramural Activities
 * DEA processes and supports the thousands of grant applications NCI receives each year and compiles reports on the progress of research funded by the NCI's programs.

Office of the director

 * Center for Biomedical Informatics and Information Technology
 * Center for Cancer Genomics
 * CCG was created in 2011 and is responsible for management of The Cancer Genome Atlas and cancer genomics initiatives.


 * Center for Cancer Training
 * Center for Global Health
 * Center for Strategic Scientific Initiatives
 * In the 1990s, the Unconventional Innovation Program was created to integrate interdisciplinary technology research with biological applications. It was reorganized in 2004 as the CSSI.


 * Center to Reduce Cancer Health Disparities
 * Center for Research Strategy
 * Coordinating Center for Clinical Trials
 * Technology Transfer Center

NCI-designated Cancer Centers
The NCI-designated Cancer Centers are one of the primary arms in the NCI's mission in supporting cancer research. There are currently 69 so-designated centers; 13 clinical cancer centers, 49 comprehensive cancer centers, and 7 basic laboratory cancer centers. NCI supports these centers with grant funding in the form of P30 Cancer Center Support Grants to support shared research resources and interdisciplinary programs. Additionally, faculty at the cancer centers receive approximately 75% of the grant funding awarded by the NCI to individual investigators.

The NCI cancer centers program was introduced in 1971 with 15 participating institutions.

National Clinical Trials Network
The NCTN was formed in 2014 from the Cooperative Group program to modernize the existing system to support precision medicine clinical trials. With precision medicine, a large number of patients must be screened to determine eligibility for treatments in development.

Lead Academic Participating Sites (LAPS) were chosen at 30 academic institutions for their ability to conduct clinical trials and screen a large number of participants and awarded grants to support the infrastructure and administration required for clinical trials. Most LAPS grant recipients are also NCI-designated cancer centers. NCTN also stores surgical tissue from patients in a nationwide network of tissue banks at various universities.

Developmental Therapeutics Program
The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents.

Under the label "Discovery & Development Services" several services are offered, among them the NCI-60 human cancer cell line screen and the Molecular Target Program.

In the Molecular Target Program thousands of molecular targets have been measured in the NCI panel of 60 human tumor cell lines. Measurements include protein levels, RNA measurements, mutation status and enzyme activity levels.

NCI-60 Human Tumor Cell Lines Screen
The evolution of strategies at the National Cancer Institute (NCI) illustrates the changes in screening that have resulted from advances in cancer biology. The Developmental Therapeutics Program (DTP) operates a tiered anti-cancer compound screening program with the goal of identifying novel chemical leads and biological mechanisms. The DTP screen is a three phase screen which includes: an initial screen which first involves a single dose cytotoxicity screen with the 60 cell line assay. Those passing certain thresholds are subjected to a 5 dose screen of the same 60 cell-line panel to determine a more detailed picture of the biological activity. A second phase screen establishes the Maximum Tolerable Dosage and involves in vivo examination of tumor regression using the Hollow fiber assay. The third phase of the study is the human tumor xenograft evaluation.[1]

Active compounds are selected for testing based on several criteria: disease type specificity in the in vitro assay, unique structure, potency, and demonstration of a unique pattern of cellular cytotoxicity or cytostasis, indicating a unique mechanism of action or intracellular target.

A high correlation of cytotoxicity with compounds of known biological mechanism is often predictive of the drugs mechanism of action and thus a tool to aid in the drug development and testing. It also tells if there is any unique response of the drug which is not similar to any of the standard prototype compounds in the NCI database.

Notable NCI faculty

 * Kathryn Zoon, Principal Deputy Director, 2002 to 2004.
 * Michael B. Sporn was the Chief of the Laboratory of Chemoprevention, 1978 to 1995.
 * Susan Gottesman
 * Sankar Adhya
 * Ira Pastan
 * Elaine Jaffe
 * Michael Gottesman
 * Robert C. Gallo
 * Michael Potter
 * Sandra Wolin

General references

 * National Cancer Institute Retrieved 11 June 2010.
 * "NCI MISSION STATEMENT." National Cancer Institute. Retrieved 18 August 2004.
 * "THE NATIONAL CANCER ACT OF 1971." National Cancer Institute. Retrieved 18 August 2004.
 * Developmental Therapeutics Program (DTP)