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http://dx.doi.org/10.13160/ricns.2011.4.1.023

Modulation of Multidrug Resistance in Cancer by P-Glycoprotein  

Gadhe, Changdev G. (Department of Bio-New Drug Development, College of Medicine, Chosun University)
Cho, Seung Joo (Department of Bio-New Drug Development, College of Medicine, Chosun University)
Publication Information
Journal of Integrative Natural Science / v.4, no.1, 2011 , pp. 23-30 More about this Journal
Abstract
Multidrug resistance (MDR) is one of the main obstacles in the chemotherapy of cancer. MDR is associated with the over expression of P-glycoprotein (P-gp), resulting in increased efflux of chemotherapy from cancer cells. Inhibiting P-gp as a method to reverse MDR in cancer patients has been studied extensively, but the results have generally been disappointing. First-generation agents were limited by unacceptable toxicity, whereas second-generation agents had better tolerability but were confounded by unpredictable pharmacokinetic interactions and interactions with other transporter proteins. Third-generation inhibitors have high potency and specificity for P-gp. Furthermore, pharmacokinetic studies to date have shown no appreciable impact on drug metabolism and no clinically significant drug interactions with common chemotherapy agents. Third-generation P-gp inhibitors have shown promise in clinical trials. The continued development of these agents may establish the true therapeutic potential of P-gp-mediated MDR reversal.
Keywords
ABC transporter; Multidrug resistance; P-glycoprotein; P-gp modulators;
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