Development of drugs to overcome drug resistance--basic approaches

P-glycoprotein plays a key role in the mechanisms of multidrug resistance in experimental tumors as well as in clinical tumors both in acquired and intrinsic-type resistance. Thus the therapeutic approaches targeting P-glycoprotein would provide benefits in eradication of drug-resistant tumor cells, although some potential problems concerning side effects still remain to be studied. Practical approaches to overcoming multidrug resistance by targeting the P-glycoprotein would be (1) to use antibodies against P-glycoprotein; and (2) to use agents, including calcium channel blocker-related agents and membrane-modifying agents, that interact with P-glycoprotein. These therapeutic approaches will be discussed in the symposium.