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Associations Between ABCC2 Polymorphisms and Cisplatin Disposition and Efficacy
Author(s) -
Sprowl J A,
Gregorc V,
Lazzari C,
Mathijssen R H,
Loos W J,
Sparreboom A
Publication year - 2012
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2011.330
Subject(s) - multidrug resistance associated protein 2 , cisplatin , pharmacology , clinical pharmacology , transporter , pharmacokinetics , single nucleotide polymorphism , toxicity , drug , adme , disposition , atp binding cassette transporter , medicine , chemistry , genotype , biochemistry , gene , chemotherapy , psychology , social psychology
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. Clinical Pharmacology & Therapeutics (2012); 91 6, 1022–1026. doi: 10.1038/clpt.2011.330