[Multidrug or pleiotropic resistance]

The resistance to cytotoxic drugs represents a major obstacle to successful cancer therapy. The intrinsic resistance of tumoral cells is one of major causes of treatment failure. The overexpression of a membrane associated glycoprotein, P-glycoprotein, in tumoral cell lines, resistant to a wide range of drugs, permitted the description of a multidrug resistance (MDR) phenotype. This P-glycoprotein, which appears to play a role in drug efflux is encoded by the mdr1 gene in humans. The frequent mdr1 gene overexpression in clinically resistant tumours suggest that this gene may be the cause of treatment failure in human cancer. This review summarizes recent developments in this area, which suggest that both the activity of the pump and its genetic regulation are potential targets for new anticancer therapies.