Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy

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

doi:10.1038/clpt.2011.330

Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy

J. A. Sprowl
, V. Gregorc
, C. Lazzari
, R. H. Mathijssen
, W. J. Loos
, A. Sparreboom

Pharmaceutical Sciences

Scientific Institute University Hospital San Rafaele
Erasmus University Rotterdam
St. Jude Children Research Hospital

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

29 Scopus citations

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	English
Pages (from-to)	1022-1026
Number of pages	5
Journal	Clinical Pharmacology and Therapeutics
Volume	91
Issue number	6
DOIs	https://doi.org/10.1038/clpt.2011.330
State	Published - Jun 2012

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10.1038/clpt.2011.330

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title = "Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy",

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, J. A.

AU - Gregorc, V.

AU - Lazzari, C.

AU - Mathijssen, R. H.

AU - Loos, W. J.

AU - Sparreboom, A.

PY - 2012/6

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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.

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Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy

Abstract

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