Resistance to alkylating agents and cisplatin: insights from ovarian carcinoma model systems

Abstract

The curative potential of chemotherapy for ovarian cancer is frequently not realized due to platinum and alkylating agent resistance. Mechanisms which may contribute to the resistant phenotype include alterations in drug transport, increased levels of sulfhydryl molecules (and/or related enzymes), and enhanced DNA repair. We have developed several ovarian cancer cell lines resistant to platinum compounds and alkylating agents. Increased levels of glutathione and enhanced DNA repair are major determinants of chemoresistance in these cells. Modulation of these processes with buthionine sulfoximine (BSO), aphidicolin, arc-C, etc. partially reverses in vitro resistance. Similar clinical treatment strategies are under investigation.