Molecular Carcinogenesis and Chemoprevention
Karam El-Bayoumy, Ph.D., Program Leader
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. More recent studies are now providing new information linking tobacco smoking with breast, colon, and prostate cancers. 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. To reduce the incidence and mortality of major cancers, leads from epidemiological studies direct our basic research activities toward:
- Elucidating the mechanisms by which chemicals, found in tobacco smoke, diet and urban air pollution alone and in combination with HPV on the induction of select cancers. Carcinogenesis is a multi-step process that takes 20-30 years in people, and in this program, we focus on understanding the molecular pathways by which normal cells progress to the first definable stage of cancer.
- Identifying sensitive and selective intermediate biomarkers in preclinical investigations (e.g, laboratory animals) as useful tools for the assessment of human exposure and risk assessment to cancer causing agents; and
- Developing mechanism-based chemopreventive agents and dietary components that can inhibit specific molecular targets involved in the carcinogenic process.
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 future 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.