A copper connection to the uptake of platinum anticancer drugs

摘要

Cisplatin [cis-diamminedichloroplati-num (II)] is a highly active anticancer agent. This agent is curative against most testicular cancers and is highly active against a wide range of other tumor types, notably ovarian, bladder carcinoma, and non-small-cell lung cancer (1). Treatment failure is frequently caused by the development of resistance to cisplatin. Although the insensitive tumors generally exhibit only low-level resistance, the use of cisplatin at close to its maximally tolerated dose implies that the developed resistance eliminates cisplatin as an active compound. Resistance to cisplatin has been widely studied in a variety of models and in clinical samples, but it has been difficult to identify the molecular changes leading to drug resistance. Ishida et al. (2) report in this issue of PNAS the identification of an important pathway for uptake of cisplatin into yeast and mammalian cells, uptake mediated by a high-affinity copper transporter.