Professor, Pharmacology & Chemical Biology
University of Pittsburgh
Elevated levels of estrogens are an important determinant of breast cancer risk. One way estrogen promotes tumor growth is by stimulating growth pathways that should not be active, thereby providing a survival benefit to the tumor cells over the neighboring “normal” cells. Another way is through production of chemical metabolites called quinones that are known to cause oxidative DNA damage. Biomarkers of DNA damage measured in urine have been used to establish a connection between estrogen, DNA damage and the risk of breast cancer. While anti-estrogen therapies are used to block the estrogen effects on growth pathways, there is an interest in the use of antioxidants, such as sulforaphane, a plant-chemical found in cruciferous vegetables, to prevent the formation of quinone-induced DNA damage and potentially reduce the risk of breast cancer. Dr. Kensler is studying the effect of a sulforaphane-rich broccoli sprout beverage on biomarkers of DNA damage in healthy women. His focus in the coming year is to study the day-to-day variability in levels of DNA damage biomarkers in pre- and post-menopausal women to see how they change after menopause or in response to natural fluctuating estrogen levels before menopause. There is an urgent need for inexpensive and effective approaches in breast cancer prevention. Results from this study may provide a viable preventive alternative.
Thomas Kensler is Professor of Pharmacology & Chemical Biology at the University of Pittsburgh. He obtained his doctorate at MIT and trained as a postdoctoral fellow at the University of Wisconsin and at the National Cancer Institute. After 30 years on the faculty of the School of Public Health at Johns Hopkins, he moved to the University of Pittsburgh in 2010. The goal of his laboratory is to elucidate the molecular mechanisms involved in the induction of cancer by chemicals to serve as a basis for the prevention, interruption or reversal of these processes in humans. A major mechanism of protection against environmental carcinogenesis is the induction of enzymes involved in their detoxication and elimination. To translate laboratory findings to humans, his group has conducted a series of "proof-of-principle" randomized clinical trials in populations at high risk for exposures to air- and food-borne toxins and carcinogens with broccoli sprout beverages rich in the phytochemical sulforaphane. They are now developing and validating biomarkers to assess the efficacy of broccoli-based interventions to block the DNA damaging actions of reactive estrogen metabolites in the context of breast cancer prevention.
Dr. Kensler’s numerous awards include the AACR-American Cancer Society Award for Excellence in Cancer Epidemiology and Prevention, Society of Toxicology Translational Impact Award and the National Friendship Award, Beijing, China’s highest award for foreign civilians. He has published over 350 research articles. He is a former chair of the NIH Chemo-Dietary Study Section and is on the editorial board of several journals.