Modulation of multidrug resistance: a paradigm for translational clinical research.
Resistance of cancer cells is the major limitation to the success of chemotherapy. Although many mechanisms of cellular resistance to anticancer drugs have been defined, the best understood of these is multidrug resistance (MDR), caused by the multidrug transporter, P-glycoprotein (P-gp), the product of the MDR1 gene. New drugs developed specifically to inhibit P-gp and modulate MDR, such as valspodar (PSC 833 [Amdray]), are currently undergoing clinical testing. Moreover, agents designed to inhibit other mechanisms of drug resistance are currently in development, and concurrent blockade of multiple mechanisms of resistance appears to be a promising approach. Coadministration of MDR1-related chemotherapeutic drugs with an MDR modulator may enhance the bioavailability of these agents sufficiently to enable oral dosing, which would potentially be more convenient and less toxic.
Sikic
B I
BI
Stanford University School of Medicine, California, USA.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003524:Cyclosporins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D003524:Cyclosporins; C070272:valspodar