The MRP1/ABCC1 Multi-drug Transporter Protein and Cancer

The ultimate cause of treatment failure for many forms of malignant and infectious diseases is the development of resistance to a broad range of cytotoxic drugs. Hence, despite significant advances in cancer treatment, multidrug resistance (MDR) remains a major clinical problem and leads to limited therapeutic options and poor patient outcome in a number of cancers, including high-risk neuroblastoma, leukaemia and carcinomas of the prostate, breast, lung and ovary. Therefore, gaining a better understanding of the mechanisms that lead to drug resistance is of utmost importance in order to improve the current chemotherapy regimes in cancer treatment. While MDR may develop in response to a specific drug or drug combination, the resultant phenotype typically confers resistance to a variety of agents, often with diverse mechanisms of action. A large body of research devoted to exploring cellular MDR has revealed that resistance most commonly arises through (a) insufficient uptake of water-soluble drugs by specific transporters, (b) alterations in cellular pathways that result in a reduced capacity of cytotoxic drugs to kill cells, or (c) increased drug efflux from cancer cells. This review deals with the latter of these mechanisms, which is most commonly associated with overexpression of one or more membrane-bound transporter proteins that act as extrusion pumps for a diverse array of substrates (1,2).