Topoisomerase I inhibitors and drug resistance

DNA topoisomerase I is a nuclear enzyme which catalyzes the conversion of t he DNA topology by introducing single-strand breaks into the DNA molecule. This enzyme represents a novel and distinct molecule target for cancer ther apy by antitopoisomerase drugs belonging to the campthotecin series of anti neoplastics. As many tumors can acquire resistance to drug treatment and be come refractary to the chemotherapy it is very important to investigate the mechanisms involved in such a drug resistance for circumventing the phenom enon. This article describes the role of topoisomerase I in cell functions and th e methods used to assess its in vitro catalytic activity. It reviews the me chanisms of cytotoxicity of the most specific antitopoisomerase I drugs by considering also the phenomenon of drug resistance. Some factors useful to drive the future perspectives in the development of new topoisomerase I inh ibitors are also evidenced and discussed.