DF/HCC Program Affiliation

Gynecologic Cancers, Co-Leader

DF/HCC Associations

Member, Center Scientific Council

Research Abstract

I conduct a large clinical and basic research effort designed to improve the therapy of patients with gynecologic malignancies such as epithelial ovarian cancer. We are active in several areas of investigation, including overcoming drug resistance, developing novel inhibitors of angiogenesis, as well as using microarray gene expression profiling in order to better understand the mechanisms of aggressive tumor behavior and resistance to chemotherapy. We have discovered that abnormalities in the pathway of programmed cell death, or apoptosis, may explain at least some of the resistance observed with paclitaxel (Taxol TM), one of the most active agents used in the treatment of patients with this disease. Specifically, we have observed that tumor cells which lack expression of the BAX pro-apoptotic protein are relatively resistant to paclitaxel, both in vitro and in the clinic, and that low levels of BAX predict for inferior response rates and disease-free survivals. By using microarray technology, we have identified a unique gene signature referred to as the OCPP, which is a powerful prognostic tool that is providing insight into the natural history of ovarian cancer. In addition to offerring patients the opportunity to participate in novel clinical trials using conventional cytotoxic agents and well as anti-angiogenesis drugs, we are also working on vaccine-based strategies in an attempt to overcome drug resistance and to eradicate minimal residual disease after completion of first-line chemotherapy. It is hoped that a combination of these approaches will eventually lead to improvements in survival for women with gynecologic malignancies.

Publications

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