Role of copper transporters in the uptake and efflux of platinum containing drugs

Cellular mechanisms for the uptake, intracellular distribution and efflux of the platinum (Pt) containing compounds cisplatin (DDP), carboplatin (CBDCA) and oxaliplatin (LOHP) are unknown. Current data suggest that specialized transporters/carriers mediate the transport of Pt drugs across the cellular membranes. Specific roles for the copper (Cu) transporters CTR1, ATP7A and ATP7B have been demonstrated during recent years. The finding that in cultured cells and tumor samples a correlation can be found between the expression of Cu transporters and the degree of the acquired resistance to Pt drug suggests that the Cu transporters are important constituents of the program that regulates sensitivity to Pt drugs. A model is presented that describes the function of Cu transporters in the regulation of Pt drug uptake and efflux.