CHEMOTHERAPY RESISTANCE IN OVARIAN-CANCER - NEW MOLECULAR PERSPECTIVES

Objective: To provide the obstetrician-gynecologist with the recent ad vances in mechanisms of chemotherapy resistance in ovarian cancer. Dat a Sources: A computerized search of articles published through Septemb er 1997 was performed on the MEDLINE Ovid and Cancerlit databases. Add itional references were identified from the reference section of all s elected papers. Methods of Study Selection: All identified references were evaluated as to their relevant contribution to our understanding of the basic mechanisms underlying the response to chemotherapy, the d evelopment of chemotherapy resistance in ovarian cancer, and possible strategies for therapy. Tabulation, Integration, and Results: One hund red sixteen references were reviewed. A brief summary of the classic c oncepts on resistance to cisplatin and paclitaxel is provided, followe d by a description of the basic mechanisms governing apoptosis and cel l cycle arrest as well as their involvement in cell response to chemot herapy and the development of chemoresistance. Finally, a brief summar y of the molecular alterations described in ovarian cancer, together w ith hypothetic strategies for gene-targeted therapy, are reported. Con clusion: Cisplatin or paclitaxel chemotherapy induces arrest of the ce ll cycle or apoptosis in ovarian cancer cells. Tumor suppressor genes such as p53 play a paramount role in mediating this response and p21(W AF1/CIP1) is a major mediator of p53-induced arrest of the cell cycle. Molecular alterations involving these tumor suppressor genes are rela ted to the development of resistance to chemotherapy and represent pos sible targets for gene therapy in ovarian cancer. (C) 1998 by The Amer ican College of Obstetricians and Gynecologists.