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Membrane transporters as determinants of the pharmacology of platinum anticancer drugs

Citation

Liu, JJ and Lu, J and McKeage, MJ, Membrane transporters as determinants of the pharmacology of platinum anticancer drugs, Current Cancer Drug Targets, 12, (8) pp. 962-986. ISSN 1568-0096 (2012) [Refereed Article]


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Copyright Statement

Copyright 2012 Bentham Science Publishers

Official URL: http://www.benthamscience.com/

DOI: doi:10.2174/156800912803251199

Abstract

Abstract: Membrane transporters govern the movement of drugs and their metabolites across biological membranes, thereby determining their pharmacokinetics, efficacy and adverse drug reactions. Platinum-based anticancer drugs are a mainstay of chemotherapy for many human malignancies. However, their clinical utility is limited by tumor resistance and normal tissue toxicities, which are determined at least in part by the level of tissue accumulation of platinum. Recently, several members of the ATP-binding cassette (ABC), solute carrier (SLC) and ATPase membrane protein superfamilies have been found to contribute to the net accumulation of platinum drugs in malignant and normal tissues. Herein, a review has been carried out to critically evaluate current preclinical and clinical evidence implicating membrane transporters as determinants of the pharmacology of cisplatin, oxaliplatin, carboplatin and related investigational compounds. The evidence includes studies of recombinant cell systems with genetically modified expression of individual membrane transporters, platinum-resistant or -sensitive human cancer cells and in vivo xenografted tumors, animal models of platinum-induced nephro-, oto- or neurotoxicity, and clinical studies of associations between the membrane transporter tumor expression and patient outcomes from platinum-based chemotherapy. Understanding the role of membrane transporters as determinants of the pharmacology of platinum drugs will be a basis for targeting these drug transporters in individualized and optimized platinum-based cancer therapy, and new drug development.

Item Details

Item Type:Refereed Article
Keywords:ABC transporter, solute carrier transporter, platinum anticancer drug
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Clinical Pharmacology and Therapeutics
Objective Division:Health
Objective Group:Other Health
Objective Field:Health not elsewhere classified
Author:Liu, JJ (Dr Johnson Liu)
ID Code:86350
Year Published:2012
Web of Science® Times Cited:39
Deposited By:Pharmacy
Deposited On:2013-09-06
Last Modified:2014-04-17
Downloads:5 View Download Statistics

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