Document Detail


Membrane Transporters as Determinants of the Pharmacology of Platinum Anticancer Drugs.
MedLine Citation:
PMID:  22794121     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Johnson J Liu; Jun Lu; Mark J McKeage
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-12
Journal Detail:
Title:  Current cancer drug targets     Volume:  -     ISSN:  1873-5576     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101094211     Medline TA:  Curr Cancer Drug Targets     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmacology and Clinical Pharmacology, and the Auckland Cancer Society Research Centre, School of Medical Sciences, Faculty of Medical and Health Sciences, The University of Auckland 1142, 85 Park Road, Grafton, Auckland, New Zealand. j.liu@auckland.ac.nz.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Pertussis vaccination in child care workers: room for improvement in coverage, policy and practice.
Next Document:  Effect of Altered WIG-1 Expression on DDP Sensitivity in a DDP-Resistant Esophageal Squamous Cancer ...