National Cancer Institute

The National Cancer Institute (NCI) coordinates the United States National Cancer Program and 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 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.

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^[6] at Fort Detrick, in Frederick, Maryland. The NCI receives more than US$5 billion in funding each year.^[7]

The NCI supports a nationwide network of 71 NCI-designated Cancer Centers with a dedicated focus on cancer research and treatment^[8] and maintains the National Clinical Trials Network.^[9]

History[edit]

Timeline[edit]

An early wooden sign for the National Cancer Institute

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.^{[10][11][12][13]}
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 US$10 billion in additional funding for the NIH; the NCI received US$1.3 billion from that amount.
2016: The 21st Century Cures Act increased funding for biomedical research. The "Cancer Moonshot" program promised additional support for cancer research.^[14]
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.^[15] He returned to the institute in November 2019 as director.^[16]

Anti-cancer drug investigations[edit]

Alkylating agents

Cyclophosphamide

Chlorambucil (Leukeran) (1957)
Cyclophosphamide (Cytoxan) (1959)
Thiotepa (1959)
Melphalan (Alkeran) (1959) (IV in 1993)
Streptozotocin (Zanosar) (1982)
Ifosfamide (Ifex) (1988)

Antimetabolites

Plant alkaloids and antibiotics

Vincristine

Synthetic drugs

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

Biologicals

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

Organization[edit]

The NCI is divided into several divisions and centers.^[17]

Intramural[edit]

Center for Cancer Research

The CCR includes approximately 250 internal NCI research groups in Frederick and Bethesda.^[18]

Division of Cancer Epidemiology and Genetics

DCEG is divided into the Epidemiology and Biostatistics Program and the Human Genetics Program.^[19]

Extramural[edit]

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.^[20] "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.^[21]

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.^[22]

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.^[23]

Office of the director[edit]

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.^[24]

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

Programs[edit]

NCI-designated Cancer Centers[edit]

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.^[8][25]

The NCI cancer centers program was introduced in 1971 with 15 participating institutions.^[26]

National Clinical Trials Network[edit]

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, 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.^[9] NCTN also stores surgical tissue from patients in a nationwide network of tissue banks at various universities.

Developmental Therapeutics Program[edit]

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.^[27]

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.^[28]

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.^[29]

NCI-60 Human Tumor Cell Lines Screen[edit]

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.

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[edit]

Director

Tenure

Notes

Carl Voegtlin^[30]

1938–1943

Roscoe Roy Spencer

1943–1947

Leonard Andrew Scheele

1947–1948

Served as the seventh Surgeon General of the United States from 1948 to 1956.

John Roderick Heller

1948–1960

Kenneth Millo Endicott

1960–1969

Carl Gwin Baker

1970–1972

Frank Joseph Rauscher, Jr.

1972–1976

Arthur Canfield Upton

1977–1980

Vincent T. DeVita, Jr.

1980–1988

Samuel Broder

1988–1995

Richard D. Klausner

1995–2001

11th Director, left to become President of the Case Institute of Health, Science, and Technology and later Executive Director of Global Health for the Bill & Melinda Gates Foundation.^[31]

Andrew C. von Eschenbach

2002–2006

12th Director, served from 2001 to 2006 before transitioning to a role as Commissioner of Food and Drugs.^[32][33]

John E. Niederhuber

2006–2010

13th Director of the NCI, was nominated by President George W. Bush.^[34]

Harold Varmus

2010–2015

Co-winner of the Nobel Prize for studies of the genetic basis of cancer.^[35] He was director of the National Institutes of Health from 1993 to 1999.

Norman E. Sharpless

October 2017–Present

15th Director of the NCI.^[36][37] Transitioned to acting Commissioner of Food and Drugs in April 2019 and returned to NCI in November 2019.^[38]