Journal
DRUG RESISTANCE UPDATES
Volume 14, Issue 1, Pages 22-34Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.drup.2010.12.002
Keywords
Platinum; Drug transporters; Solute carriers (SLCs); Organic cation transporters (OCTs); PK resistance; Cimetidine; Metformin
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Platinum-based drugs are among the most active anticancer agents and are successfully used in a wide variety of human malignancies. However, acquired and/or intrinsic resistance still represent a major limitation. Lately, in particular mechanisms leading to impaired uptake and/or decreased cellular accumulation of platinum compounds have attracted attention. In this review, we focus on the role of active platinum uptake and efflux systems as determinants of platinum sensitivity and -resistance and their contribution to platinum pharmacokinetics (PK) and pharmacodynamics (PD). First, the three mostly used platinum-based anticancer agents as well as the most promising novel platinum compounds in development are put into clinical perspective. Next, we describe the presently known potential platinum transporters - with special emphasis on organic cation transporters (OCTs) - and discuss their role on clinical outcome (i.e. efficacy and adverse events) of platinum-based chemotherapy. In addition, transporter-mediated tumour resistance, the impact of potential platinum transporter-mediated drug-drug interactions, and the role of drug transporters in the renal elimination of platinum compounds are discussed. (C) 2011 Elsevier Ltd. All rights reserved.
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