Cellular Pharmacology of Cisplatin: Perspectives on Mechanisms of Acquired Resistance

The interactions of cisplatin with DNA have been defined in sophisticated detail; however, the interactions of this drug with other components of the cell are less well understood. There is much interest in how cisplatin gets into cells, how it is transformed and inactivated, how it and its biotransformation products are effluxed from the cell, how the DNA damage is repaired, and how all of these processes can be modulated for therapeutic gain. Recent years have seen much progress toward defining the cellular pharmacology of cisplatin and, in the process, several mechanisms of acquired resistance to this drug have now been elucidated.