My academic career goal is to coordinate my clinical and research backgrounds and apply them to the prevention of cancer. As a physician with both medical oncology training and research experience, my ultimate aim is to become an independent investigator in the field of chemoprevention. A Preventive Oncology Academic Award would allow me to develop the skills necessary to design and conduct clinical chemopreventive trials, especially in the area of colorectal cancer. The Fox Chase Cancer Center offers an environment rich in both research and clinical expertise. An invaluable resource to my education will be the opportunity to work with Dr. Margie Clapper, an investigator with an excellent background in basic research, chemoprevention, and clinical trials. Peter O'Dwyer, M.D., will supervise my involvement with the Developmental Chemotherapy program which will provide further insights into the development of clinical trials. Participation at educational courses, lectures, seminars, and national meetings will increase my knowledge base and allow me to present my research. Conferences held by the Department of Medical Oncology and the Division of Population Science will be an excellent opportunity to refine my teaching skills. Educational sessions regarding chemoprevention trials will be provided for surrounding communities and their physicians. Development of a research program focusing on strategies to prevent colorectal cancer is proposed. Phase II detoxification enzymes, including glutathione S-transferase and DT-diaphorase, play a critical role in protecting the colon from numerous structurally diverse carcinogens. Preliminary studies have indicated that individuals at increased risk of developing colorectal cancer possess low levels of glutathione S- transferase. If these enzymes were elevated at the time of carcinogen exposure, the cancer-causing agent would be unable to reach its target and the early cellular events required for tumor formation would be inhibited. An excellent strategy to prevent colorectal cancer would be to develop interventions that would increase the levels of the protective detoxification enzymes. Three specific intervention projects will be undertaken. The first will address the effect of a dietary intervention with cruciferous vegetables on Phase II detoxification enzymes. The second and third studies are Phase I pharmacokinetic/biochemical trials of the chemopreventive agent Oltipraz given on a single and multiple dose schedule. Both Oltipraz and cruciferous vegetables have been selected for evaluation based upon their ability to prevent chemically induced tumors in animals and to modulate detoxification enzyme activity. These studies are anticipated to lead to future long-term chemoprevention trials.
