The goal of this preclinical program is to develop efficacious regimens for the clinical prevention of cancer. Current efforts focus on the chemoprevention of colon, lung and oral cancer. Areas of research include: 1) the identification of effective chemopreventive agents and their mechanisms of action, 2) the establishment of biomarkers of cancer susceptibility and surrogate endpoints of carcinogenesis and 3) the identification of target populations at increased risk for cancer. Biomarker analyses of biopsies from Phase I/II clinical chemoprevention trials are also performed in this laboratory.
Previous studies in both mice with colitis-associated colon cancer and individuals at increased risk for colorectal cancer have revealed an association between Phase II detoxication enzyme deficiencies and increased susceptibility for cancer. The contribution of polymorphisms in Phase I and II detoxication enzymes to cancer risk is currently being examined by characterizing populations known to be at high risk and generating genetically defined mouse models. The ability of oltipraz to inhibit colitis-associated colon cancer and pancreatic cancer has been demonstrated. The molecular basis for this chemopreventive activity remains an area of active investigation. Recent establishment of a unique multiple intestinal neoplasia (Min) mouse colony has provided an opportunity to develop novel chemopreventive strategies for individuals with mutations in the adenomatous polyposis coli (APC) gene.