Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 91, Issue 6, Pages 1022-1026Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/clpt.2011.330
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Funding
- American Lebanese Syrian Associated Charities (ALSAC)
- US Public Health Service Cancer Center [3P30CA021765]
- National Cancer Institute [5R01CA151633-01]
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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.
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