Topoisomerase I in multiple drug resistance

Topoisomerase I is a nuclear enzyme able to catalyse the relaxation of supercoiled DNA by introducing single-stranded breaks in DNA molecule. Its function seems important to prepare DNA for many processes such as recombination, DNA repair and RNA transcription. The most important drugs active as inhibitors of topoisomerase I are represented by camptothecin and its derivatives which were developed as promising anticancer drugs. Since selectivity of action is essential for an antitumor drug, many studies were performed to investigate the mechanisms by which cancer cells become resistant to drug treatment by developing a condition of multiple drug resistance (MDR). This article analyses the role of topoisomerase I in cell functions, considers the cellular effects of topo I poisons and discusses the ways by which tumoral cells may become resistant to these drugs with a special attention to MDR mechanisms.