Novel Concepts in the Development of Platinum Antitumour Drugs: An Update

The limitations of cisplatin as an anticancer drug have stimulated the search for other antitumour-active platinum complexes with improved pharmacological properties. The two main goals in the search for new platinum anticancer agents are the reduction of the dose-limiting toxicities of cisplatin and the circumvention of cisplatin resistance. However, it should be noted that this has proven to be a difficult task. In fact, less than 1% of the thousand of platinum complexes tested for pre-clinical antitumour activity have entered clinical trials in the past 30 years. Nonetheless, at present, several new platinum complexes are in clinical trials; a proof of the continued belief that platinum complexes may still fulfil the needs for novel antitumour drugs. This review will focus on the three main innovative bioinorganic approaches found in the platinum anticancer-field, namely, (1) compounds with a slowed down kinetic of activation, (2) compounds with carrier ligands, and (3) compounds that bind differently to DNA as compared to cisplatin. In the latter class, special attention is paid to dinuclear and polynuclear platinum complexes.