Associations Between  ABCC2  Polymorphisms and Cisplatin Disposition and Efficacy | Zendy

Sprowl J A | Zendy; Gregorc V | Zendy; Lazzari C | Zendy; Mathijssen R H | Zendy; Loos W J | Zendy; Sparreboom A | Zendy

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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

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