August 22, 2013

Overcoming resistance in ovarian cancer

The nuclear receptor TR3 contributes to ovarian cancer cell death in response to platinum-based chemotherapy – and may be a good target for overcoming cell resistance to certain treatments.

Ovarian cancer is most often diagnosed as aggressive, metastatic disease that is already resistant to standard platinum-based chemotherapy. The nuclear receptor TR3 has been implicated in mediating cancer cell death (apoptosis) in response to chemotherapeutic agents.

To identify possible roles for TR3 in ovarian cancer, Dineo Khabele, M.D., assistant professor of Obstetrics and Gynecology, and colleagues studied TR3 expression in a tissue microarray generated from ovarian tumor samples. The investigators found that low TR3 expression was associated with resistance to platinum chemotherapy and poorer overall survival. In cultured ovarian cancer cells, they showed that TR3 moved from the nucleus to the cytoplasm in cells that were sensitive to cisplatin, but not in resistant cells. Experimentally lowering the expression of TR3 reduced the effects of cisplatin on apoptosis and cell growth.

The findings, reported Aug. 1 in Cancer Research, suggest that disruption of TR3 activity contributes to platinum chemotherapy resistance in ovarian cancer. Increasing TR3 function may be a therapeutic strategy for overcoming this resistance.

This research was supported by grants from the National Institutes of Health (TR000445, CA068485, CA091408, RR024975, CA148887) and by the Marsha Rivkin Ovarian Cancer Foundation.