Mechanisms of Carcinogenesis and Chemoprevention

Program Leaders:  Karam El-Bayoumy, Ph.D. and Jeffrey Peters, Ph.D.

In the United States, nearly two-thirds of cancer deaths can be linked to tobacco use and diet. Tobacco consumption is directly related to cancer of the lung, mouth, larynx, esophagus, bladder, kidney, pancreas, leukemia and cervix. Studies linking tobacco smoking with breast and colorectal cancer have been reported.  Excess or deficiencies of certain dietary components can account for cancer of the colon, breast, prostate, and stomach. The predominance of environment over genes in cancer causation has been suggested. The overall research direction in this program is to uncover, by using a step-wise approach, exactly how cancer develops, and then provide the means for cancer chemoprevention. The program has two research themes:

 1.  Elucidate the molecular mechanisms of chemical and environmental-induced carcinogenesis and the impact of genetic/dietary/environmental interactions on cancer susceptibility.  The emphasis of this theme is directed toward DNA damage and repair, the role of soluble receptors, and unique mechanisms of inflammation in the carcinogenesis process.

2.  Develop mechanism-based synthetic and naturally-occurring chemopreventive agents through the identification of critical targets and determine the efficacy and mechanisms of chemopreventive agents in combination with nutritional manipulation.  The emphasis of this theme is directed toward the development of novel receptor-based compounds with antioxidant, anti-inflammatory and/or tumor-specific anti-proliferative agents for cancer chemoprevention.

Collectively, in this Program, we strive to acquire new mechanistic insights on the causes of tobacco-, dietary-, and environmentally-related cancers. Suitable biomarkers are being developed and validated for translational studies as well as the design of future clinical chemoprevention trials. Therefore, we are searching for optimal diets and for naturally occurring agents in routinely consumed foods that may inhibit cancer development. Structural modifications of established, naturally-occurring chemopreventive agents have led us to synthesize novel agents with even greater preventive capacity and lower toxicity. In our laboratories, it has been a common practice to induce predictable incidences of cancer with carcinogens present in tobacco and in our environment, and in some instances, by synthetic carcinogens to provide a yardstick for measuring cancer preventive capacity of naturally occurring or newly developed synthetic compounds.

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