Associations Between ABCC2 Polymorphisms and Cisplatin Disposition and Efficacy

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

doi:10.1038/clpt.2011.330

Associations Between ABCC2 Polymorphisms and Cisplatin Disposition and Efficacy

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

Medical Oncology

Research output: Contribution to journal › Article › Academic › peer-review

27 Citations (Scopus)

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.

Original language	Undefined/Unknown
Pages (from-to)	1022-1026
Number of pages	5
Journal	Clinical Pharmacology & Therapeutics
Volume	91
Issue number	6
DOIs	https://doi.org/10.1038/clpt.2011.330
Publication status	Published - 2012

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10.1038/clpt.2011.330

http://hdl.handle.net/1765/55371

Cite this

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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.",

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AU - Sprowl, JA

AU - Gregorc, V

AU - Lazzari, C

AU - Mathijssen, RHJ

AU - Loos, Walter

AU - Sparreboom, A

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1038/clpt.2011.330

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