Multidrug resistance in human cancer.

Resistance to cytotoxic chemotherapy continues to be a major obstacle to more effective treatment of human cancers. A particular problem in clinical cancer chemotherapy is the phenomenon of simultaneous resistance of cancers to a variety of unrelated cytotoxic agents. Such resistance to multiple drugs is observed much more often than resistance to individual compounds. A similar experimental phenomenon has been termed multidrug resistance or MDR. Much has been learned in recent years about molecular mechanisms which can lead to MDR in cancer cells and a number of studies has been performed to evaluate the clinical relevance of such mechanisms. In particular, P-glycoprotein-associated MDR (MDR1) has received a lot of attention. This review will discuss (i) some principal aspects of drug resistance in cancer with particular emphasis on MDR1; (ii) available data on drug resistance mechanisms in brain tumors; and (iii) our current knowledge on the putative role of P-glycoprotein in the blood-brain barrier.