[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.
Tsuruo
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Institute of Molecular and Cellular Biosciences, University of Tokyo.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D006801:Humans; D007941:Leukemia P388 / Q000473:pathology; D007951:Leukemia, Myeloid / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011804:Quinolines / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D011804:Quinolines; C087719:dofequidar; D016572:Cyclosporine; D014700:Verapamil