Too Much of a Good Thing: Suicide Prevention Promotes Chemoresistance in Ovarian Carcinoma

Ovarian cancer is the most lethal of gynecologic malignancies. Currently, standard treatment for epithelial ovarian cancer consists of surgical debulking followed by adjuvant chemotherapy with a platinum-based drug coupled with paclitaxel. While initial response to chemotherapy is high, the majority of patients develop recurrent disease which is characterized by chemoresistance. The primary cytotoxic effect of many chemotherapy drugs is mediated by apoptotic response in tumor cells. Recent data indicate that cross talk between the tumor microenvironment and malignant epithelial cells can influence apoptotic response as well. The identification of molecules involved in the regulation and execution of apoptosis, and their alterations in ovarian carcinoma have provided new insights into the mechanism behind the development of chemoresistance in this disease. Our challenge now is to devise strategies to circumvent cell death defects and ultimately improve response to treatment in ovarian carcinoma patients.