Platinum transporters and drug resistance.
Cisplatin, a platinum coordinated complex, is a widely used antineoplastic agent for the treatment of metastatic tumors of the testis, metastatic ovarian tumors, lung cancer, advanced bladder cancer and many other solid tumors. The cytotoxic action of the drug is often thought to be associated with its ability to bind DNA to form cisplatin-DNA adducts. The development of resistance to cisplatin during treatment is common and constitutes a major obstacle to the cure of sensitive tumors. Although to understand the clinically relevant mechanisms of resistance, many studies have been aimed at clarifying the biochemical/molecular alterations of cisplatin-resistance cells, these studies did not conclusively identify the basis of cellular resistance to cisplatin. In this review, cisplatin resistance was discussed in terms of the relevant transporters, such as copper transporters (CTRs), organic cation transporters (OCTs) and multi-drug resistance related transporters (MDRs). These transporters seem to be contributed to cisplatin resistance through the reduction of drug accumulation in the cell. Better understanding the mechanism of cisplatin resistance associated with transporters will provide the useful informations for overcoming the cisplatin resistance.
Choi
Min-Koo
MK
Department of Pharmaceutics, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Kim
Dae-Duk
DD
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002945:Cisplatin / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D019450:Genes, MDR; D006801:Humans; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D010984:Platinum / Q000378:metabolism*
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D027701:Organic Cation Transport Proteins; D010984:Platinum; D000251:Adenosine Triphosphatases; D002945:Cisplatin