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^*

^*Corresponding author for this work

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

29 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	English
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 - Jun 2012

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research programs

EMC MM-03-86-08

Access to Document

10.1038/clpt.2011.330

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

Cite this

@article{fd0d0018a3cf4cb0891fb8f5bb32bfd7,

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.",

author = "Sprowl, \{J A\} and V Gregorc and C Lazzari and Mathijssen, \{R H\} and Loos, \{W J\} and A Sparreboom",

year = "2012",

month = jun,

doi = "10.1038/clpt.2011.330",

language = "English",

volume = "91",

pages = "1022--1026",

journal = "Clinical Pharmacology \& Therapeutics",

issn = "0009-9236",

publisher = "Wiley-Blackwell",

number = "6",

}

TY - JOUR

T1 - Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy

AU - Sprowl, J A

AU - Gregorc, V

AU - Lazzari, C

AU - Mathijssen, R H

AU - Loos, W J

AU - Sparreboom, A

PY - 2012/6

Y1 - 2012/6

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

DO - 10.1038/clpt.2011.330

M3 - Article

C2 - 22534871

SN - 0009-9236

VL - 91

SP - 1022

EP - 1026

JO - Clinical Pharmacology & Therapeutics

JF - Clinical Pharmacology & Therapeutics

IS - 6

ER -

Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy

Abstract

UN SDGs

Research programs

Access to Document

Fingerprint

Cite this