Genetic Polymorphisms and Cisplatin- Related Nephrotoxicity

Abstract

Cisplatin is one of the most widely applied antineoplastic agents used to treat different types of solid tumours. However, its use is limited by serious side- effects including nephrotoxicity. Cisplatin accumulates in proximal tubule and forms nephrotoxins that causes proximal cell injury and thereby leads to nephrotoxicity. Cisplatin enters these proximal cells by organic transporter molecules (OCT). Genetic polymorphism of these molecules and other membrane transport proteins that regulate cisplatin accumulation may influence cisplatin- related nephrotoxic outcome. Variations of DNA repair enzymes, e.g., ERCC1, eIF3, MMS 19L, and metabolic enzymes involved in platinum detoxification, e.g., GSTT1, GSTM1 may also have important role in the generation of nephrotoxicity. Polymorphisms of these genes can be used as predictive tools for such adverse- events in an individual. Thus chemotherapy can be modulated accordingly without compromising with antineoplastic activities of cisplatin.