Drug resistance can occur at several levels and is the major cause of treatment failure in oncology. The ABC (ATP-binding cassette) transporters, beginning with the discovery of P-gylcoprotein (Pgp) almost 30 years ago, have been intensively studied as potential mediators of drug resistance. Although we understand that drug resistance is almost certainly multifactorial, investigators have attempted to link anticancer drug resistance to overexpression of ABC transporters and the consequent reduction in drug accumulation. A body of evidence implicated Pgp as being important in clinical outcome; however, critical studies aimed at proving the hypothesis using Pgp inhibitors in clinical trials have to date failed. Identification of the MRP (multidrug resistance protein)/ABCC subfamily expanded the possible mechanisms of reduced drug accumulation, and the discovery of ABCG2 added a new chapter in these investigations. Correlative studies examining ABCG2 and the ABCC subfamily members in clinical drug resistance have been less avidly pursued, while basic molecular studies of structure and function have proceeded briskly. Recently, studies have focused on how single nucleotide polymorphism in multidrug transporters might affect the pharmacokinetics and pharmacodynamics of anticancer agents. These studies suggest an important role for ABC transporters in pharmacology, independent of the ultimate determination of their role in multidrug resistance.
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February 2005
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Conference Article|
February 01 2005
ABC transporters in the balance: is there a role in multidrug resistance?1
O. Polgar;
O. Polgar
1Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bldg. 10, Rm. 12C103, Bethesda, MD 20892, U.S.A.
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S.E. Bates
S.E. Bates
2
1Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bldg. 10, Rm. 12C103, Bethesda, MD 20892, U.S.A.
2To whom correspondence should be addressed (email sebates@helix.nih.gov).
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Publisher: Portland Press Ltd
Received:
November 05 2004
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2005 The Biochemical Society
2005
Biochem Soc Trans (2005) 33 (1): 241–245.
Article history
Received:
November 05 2004
Citation
O. Polgar, S.E. Bates; ABC transporters in the balance: is there a role in multidrug resistance?. Biochem Soc Trans 1 February 2005; 33 (1): 241–245. doi: https://doi.org/10.1042/BST0330241
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