Drug resistance to topoisomerase II inhibitors.

We describe in this review the mechanisms of resistance to topoisomerase II inhibitors that have been identified in cell lines rendered resistant to drugs. They concern especially both quantitative and qualitative alterations of topoisomerase II, leading to drug insensitivity of the cells. Expression and activity of topoisomerase II have also been studied in a number of tumor specimens originating from patients, but the role of topoisomerase II alterations in drug resistance in the clinical setting has not yet been firmly established. It would be worthwhile, however, to develop predictive assays for drug activity in human cancers, based upon the topoisomerase II status of tumor samples.