National Cancer Institute

History

Timeline

• August 5, 1937: President Franklin D. Roosevelt signed into law the National Cancer Institute Act (Pub. Law 75-244; 50 Stat. 559), which established the National Cancer Institute, as a division of the Public Health Service.
• 1940: The first issue of the Journal of the National Cancer Institute was published.
• 1944: The United States Congress made the NCI an operating division of the National Institutes of Health by its passage of the Public Health Service Act. Congress later 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 conducted 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 Richard Nixon converted the U.S. Army's former biological warfare facilities at Fort Detrick, Maryland, to house research activities on the causes, treatment, and prevention of cancer.
• 1971: The 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, Maryland, as a Federally Funded Research and Development Center
• 1993: The NIH Revitalization Act of 1993 encourages NCI to expand its efforts in prostate cancer, breast and other cancers which primarily or solely affected women, and authorized increased appropriations.
• 1998: Establishes the Office of Cancer Complementary and Alternative Medicine to study pseudoscientific alternative medicine treatments for cancer
• 2009: The American Recovery and Reinvestment Act of 2009 provided in additional funding for the NIH; the NCI received from that amount.
• 2016: The 21st Century Cures Act increased funding for biomedical research. The "Cancer Moonshot" program promised additional support for cancer research.
• On October 17, 2017, Norman Sharpless was sworn in as the 15th director of the National Cancer Institute. In April 2019, Sharpless left NCI to serve as the acting Commissioner of Food and Drugs. He returned to the institute in November 2019 as director.

Anti-cancer drug investigations

Alkylating agents [[Image:Cyclophosphamide structure.svg|right|thumb|96px|[[Cyclophosphamide]]]]

• 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 [[Image:Vincristine.svg|right|thumb|114px|[[Vincristine]]]]

• 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)

Plant flavonoids

• chrysin quercetin galangin naringenin (1994)}} Synthetic drugs [[File:Carboplatin-2D-skeletal.png|thumb|107px|[[Carboplatin]]]]
• 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 made up of eight branches within the Trans-divisional Research 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

Programs

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 73 so-designated centers; 9 cancer centers, 57 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 National Clinical Trials Network (NCTN) was formed in 2014, from the Cooperative Group program to modernize the existing system to support precision medicine clinical trials. With precision medicine, many 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. |access-date= 6 January 2018

Discovery & Development ServicesUnder the label "Discovery & Development Services" several services are offered, among them the NCI-60 human cancer cell line screen and the Molecular Target Program.{{cite web |access-date= 6 January 2018 |archive-date= 9 July 2017 |archive-url= https://web.archive.org/web/20170709235548/https://dtp.cancer.gov/discovery_development/default.htm |url-status= dead

Molecular Target ProgramIn 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. |access-date= 7 January 2018

NCI-60 Human Tumor Cell Lines Screen

The evolution of strategies at the 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.

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.

Leadership

List of NCI directors since 1937:

Table notes:

Notable NCI faculty

• Amy Berrington de González, senior investigator and radiation epidemiology branch chief.
• Kathryn Zoon, Principal Deputy Director, 2002 to 2004.
• Michael B. Sporn was the Chief of the Laboratory of Chemoprevention, 1978 to 1995.
• Tom Misteli, NIH Distinguished Investigator and Director of the NCI Center for Cancer Research
• Susan Gottesman
• Sankar Adhya
• Ira Pastan
• Elaine Jaffe
• Michael Gottesman
• Robert C. Gallo
• Rosandra N. Kaplan, head of the tumor microenvironment and metastasis branch
• Michael Potter
• Sandra Wolin
• Charles J. Sherr
• Louis M. Staudt
• Gordon Zubrod
• Steven Rosenberg
• Alfred Singer, Chief of the Experimental Immunology Branch of the National Cancer Institute
• Xiaohong Rose Yang, senior investigator.
• Douglas R. Lowy, Chief, Laboratory of Cellular Oncology; NCI Principal Deputy Director, initial development, characterization, and clinical testing of the preventive virus-like particle-based HPV vaccines.

Notable people

• Susan Shurin, senior adviser
• Sudhir Srivastava, chief scientist at Cancer Biomarkers Research Group of the Division of Cancer Prevention
• Catharine West and Barry Rosenstein, lead investigators for the Radio-Genomics Consortium (established 2009)

References

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