Recent advances in P-glycoprotein-mediated multidrug resistance reversal mechanisms.

Expression of the multidrug resistance (MDR) phenotype is responsible for chemotherapy failure in numerous cancers. Overexpression of mdr1 gene-encoded permeability glycoprotein (P-gp) is known to play a pivotal role in the development of this phenotype. The role of P-gp has been proposed as an important goal in the design of chemotherapy strategies. However, modulation of P-gp activity by chemotherapy has limited possibilities because of toxicity and poor specificity. In this article, we review the latest advancements in different potential P-gp-mediated MDR reversal mechanisms as well as the methods of evaluating MDR reversal activity, which would be helpful in finding novel MDR reversal agents (or chemosensitizers).