Prostate cancer chemoprevention agent development: the National Cancer Institute, Division of Cancer Prevention portfolio.
OBJECTIVE
We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used.


METHODS
The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models.


RESULTS
Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention.


CONCLUSIONS
Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute.
Parnes
Howard L
HL
Prostate and Urologic Cancer Researh Group, Division of Cancer Prevention, National Cancer Institute, National Institute of Health, Bethesda, Maryland, USA.
House
Margaret G
MG
Kagan
Jacob
J
Kausal
David J
DJ
Lieberman
Ronald
R
D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D006801:Humans; D008297:Male; D009316:National Institutes of Health (U.S.); D011471:Prostatic Neoplasms / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D014481:United States
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor