Associations Between ABCC2 Polymorphisms and Cisplatin Disposition and Efficacy

JA Sprowl, V Gregorc, C Lazzari, RHJ Mathijssen, Walter Loos, A Sparreboom

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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.
Original languageUndefined/Unknown
Pages (from-to)1022-1026
Number of pages5
JournalClinical Pharmacology & Therapeutics
Issue number6
Publication statusPublished - 2012

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