Chemoprevention of Ovarian Cancer: Molecular Mechanisms and Markers

Principal Investigator: Robert C. Bast, Jr., M.D.

Clinical and laboratory studies suggest that oral contraceptives and derivatives of vitamin A may help to prevent ovarian cancer. Oral contraceptives may act, in part, by decreasing the number of times a woman ovulates, thus reducing the amount of wear and tear on the ovarian surface cells. By decreasing the number of times that ovarian surface cells divide, the number of genetic mistakes may be reduced. In addition, both oral contraceptives and vitamin A derivatives may drive both normal and abnormal cells on the ovarian surface to self-destruct. This process may purge the ovarian surface of genetically damaged cells and reduce the chance that a single cell could sustain sufficient genetic damage to give rise to a cancer.

This grant will explore the factors that contribute to the elimination of ovarian surface cells, studying the role of a natural growth inhibitor, transforming growth factor beta (TGFß) and its interaction with vitamin A derivatives and the hormones that are contained in oral contraceptives (estrogen and progestin). Portions of ovaries will be grown outside the body and treated with each of these factors, individually and in combination. Effects on the production of TGFß, the self-destruction of ovarian surface cells and the activation or deactivation of different genes will be studied.

The ability of normal ovarian cells, dying ovarian cells and ovarian cancer cells to absorb and scatter light will be measured in an attempt to develop a method for detection of abnormal cells on the surface of the ovary and the inner surface of the abdominal wall in women at risk for developing ovarian cancer. Use of laser light may permit monitoring of the use of drugs to prevent ovarian cancer and may detect ovarian cancer at an early interval when it can be more readily cured.

Key Words: Chemoprevention, biomarkers, oral contraceptives, 4-HPR, fluorescence spectroscopy