Stephen A. Cannistra, MD
Professor, Department of Medicine, Harvard Medical School
Director, Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center
Attending Physician, Medical Oncology Service, Dana-Farber Cancer Institute
DF/HCC Program AffiliationGynecologic Cancers
Member, Clinical Science Coordinating Committee
The goal of my research and clinical efforts is to improve the therapy of patients with gynecologic malignancies such as epithelial ovarian cancer. Our program conducts several areas of investigation in a variety of relevant areas including drug resistance, angiogenesis, homologous recombination, and immune checkpoint regulation in ovarian cancer. 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 that 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 unique gene signatures that may have important prognostic value, as well as predictive value in identifying patients more likely to response to PARP inhibitors. Through our clinical investigation efforts we have defined an important role for anti-angiogenic therapy in ovarian cancer treatment (bevacizumab) and have expanded these observations by developing preclinical models that allow us to better understand the anti-angiogenic potential of thrombospondin derivatives in this disease. Finally, we have been investigating the pathways involved in immune checkpoint regulation, specifically related to PD-L1 expression in ovarian cancer, in order to better predict which patients may benefit from therapies that specifically interfere with this process (such as antibodies against CTLA-4, PD-1, and PD-L1). It is hoped that a combination of these approaches will eventually lead to improvements in survival for women with gynecologic malignancies.
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