Platinum drugs, copper transporters and copper chelators

Increased drug resistance is associated to down-regulation of CTR1 and up-regulation of Cu-ATPases and Cu-chaperone Atox1, which is crucial for Cu secretion. The ability of Cu-lowering agents, such as tetrathiomolybdate, to increase cisplatin uptake, down-regulate Cu-ATPases and inhibit platination of Cu-Atox1 may resensitize cisplatin-resistant cells and improve the treatment efficacy of platinum drugs.