Mechanisms of resistance to alkylating agents

摘要: Alkylating agents are the most widely used anticancer drugs whose main target is DNA, although how exactly DNA lesions cause cell death still not clear. The emergence of resistance to this class as well other antitumor one major causes failure cancer treatment. This paper reviews some best characterized mechanisms alkylating agents. Pre- and post-target recognized, former able limit formation lethal adducts, latter enabling repair or tolerate damage. role in pre-target reduced drug accumulation increased detoxification activation systems (such DT-diaphorase, metallothionein, GST/GSH system, etc...) discussed. In different pathways, tolerance alkylation damage ‘downstream’ effects (cell cycle arrest and/or apoptosis) examined.