This program, established more than 20 years ago, is one of the first basic research programs nationally to focus on the development of strategies for the prevention of cancer. Its overall goal is to develop novel, efficacious preventive regimens for those individuals who are at highest risk for cancer, based on predisposing genetic and environmental factors. All research is highly translational, with experimentation spanning from cultured cells and genetically-defined animal models to the analysis of human tissues and conduct of clinical trials. Innovative use of state-of-the-art genomic and image-based technologies continues to provide unique insight into the molecular basis for cancer susceptibility and inform the design of promising strategies for early tumor inhibition. As a Prime Contractor of the Division of Cancer Prevention, NCI for the past two decades, the group has evaluated the ability of numerous promising agents to inhibit tumor formation in preclinical animal models and comprehensively investigated the associated mechanisms of drug action. Specific research interests include the establishment of regimens for the prevention of colorectal cancer in high?risk subjects with ulcerative colitis or predisposing genetic factors, the improved detection of early colorectal tumors, and the contribution of hormones to the development of lung cancer among never-smokers. In many cases, findings from preclinical efficacy and mechanistic studies have led to the conduct of biomarker trials in humans with promising cancer preventive agents. The laboratory has been funded continuously by grants from the National Cancer Institute, NIH since its initiation and has a long track record of mentoring talented physician scientists, and pre- and postdoctoral trainees.