Perspectives Genetics of Multidrug Resistance

Despite major advances in the treatment of cancer, resistance to multiple chemotherapeutic agents remains a major cause of treatment failure. Some tumors are initially resistant to many of the most active antineoplastic agents. Other tumors that are initially sensitive to cytotoxic agents often recur and fre-quently develop resistance to a broad range ofchemotherapeu-tic agents including those used during the initial therapy. Both the intrinsic and acquired resistance to chemotherapeutic agents have been inherently difficult to study in the clinical setting. However, drug-resistant cell lines have provided a tool for studying the mechanisms underlying resistance to the drugs used in chemotherapy. Although drug-resistant cell lines are usually derived by selection for resistance to a single cyto-toxic agent, they often develop cross-resistance to a broad spectrum of structurally and functionally unrelated com