Intracellular Trafficking of MDR Transporters and Relevance of SNPs

Author(s): Letizia Porcelli, Clara Lemos, Godefridus J. Peters, Angelo Paradiso, Amalia Azzariti.

Journal Name: Current Topics in Medicinal Chemistry

Volume 9 , Issue 2 , 2009

Abstract:

Multi-drug resistance (MDR) frequently contributes to the failure of chemotherapeutic treatments in cancer patients. Mechanisms underlying the development of MDR have been extensively studied and are considered multifactorial. Among them, the ATP-Binding Cassette (ABC) family of proteins plays a pivotal role. Processes of cellular distribution and subcellular localization of MDR-ABC proteins are not yet well explored and to enlighten these topics could be crucial to understand cellular drug uptake and retention. In this review, we analysed literature data concerning i) intracellular trafficking of MDR-ABC proteins (BCRP, P-gp and MRP1) and ii) mechanisms altering their cellular localization and trafficking. Moreover, we describe single nucleotide polymorphisms (SNP) that have been reported for some multidrug resistance (MDR) transporters, such as BCRP and P-gp, emphasizing their ability to affect the expression, function and localization of the transporters, with implications on drug resistance phenotypes.

Keywords: P-gP, MDR, MRP, BCRP, SNP

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Article Details

VOLUME: 9
ISSUE: 2
Year: 2009
Page: [197 - 208]
Pages: 12
DOI: 10.2174/156802609787521562
Price: $58

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