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Clin Pharmacol Ther. 2012 Jun;91(6):1022-6. doi: 10.1038/clpt.2011.330.

Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy.

Author information

1
Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.

Abstract

ABCC2 (MRP2, cMOAT) expression has been implicated in cisplatin resistance in vitro. In mice, cisplatin disposition and toxicity were unaffected by Abcc2 knockout (Abcc2−/−). Moreover, in cancer patients (n = 237), cisplatin pharmacokinetics (P > 0.12) and efficacy (P > 0.41) were not associated with seven of the single-nucleotide polymorphisms (SNPs) in ABCC2. These SNPs were also not correlated with ABCC2 expression in the NCI60 panel (P > 0.26) or with cisplatin-induced cytotoxicity (P = 0.21). These findings highlight the importance of verifying drug-transporter interactions with in vitro tests in humans.

PMID:
22534871
PMCID:
PMC3482956
DOI:
10.1038/clpt.2011.330
[Indexed for MEDLINE]
Free PMC Article

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