The importance of
platinum drugs in
cancer chemotherapy is underscored by the clinical success of
cisplatin [
cis-diamminedichloroplatinum(II)] and its analogues and by clinical trials of other, less toxic
platinum complexes that are active against resistant
tumors. The antitumor effect of
platinum complexes is believed to result from their ability to form various types of adducts with
DNA. Nevertheless, drug resistance can occur by several ways: increased drug efflux, drug inactivation, alterations in drug target, processing of drug-induced damage, and evasion of apoptosis. This review focuses on mechanisms of resistance and sensitivity of
tumors to conventional
cisplatin associated with
DNA modifications. We also discuss molecular mechanisms underlying resistance and sensitivity of
tumors to the new
platinum compounds synthesized with the goal to overcome resistance of
tumors to established
platinum drugs. Importantly, a number of new
platinum compounds were designed to test the hypothesis that there is a correlation between the extent of resistance of
tumors to these agents and their ability to induce a certain kind of damage or conformational change in
DNA. Hence, information on
DNA-binding modes, as well as recognition and repair of DNA damage is discussed, since this information may be exploited for improved structure-activity relationships.