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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacokinetics*
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Antineoplastic Agents / therapeutic use*
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Cell Line, Tumor
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Cisplatin / adverse effects
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Cisplatin / pharmacokinetics*
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Cisplatin / therapeutic use*
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Cohort Studies
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DNA / genetics
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Genetic Variation
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Humans
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Kidney Diseases / chemically induced
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Mice
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Mice, Knockout
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins / genetics*
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Polymorphism, Genetic
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Polymorphism, Single Nucleotide
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RNA / genetics
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Real-Time Polymerase Chain Reaction
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White People
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Whole Body Imaging
Substances
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ABCC2 protein, human
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Antineoplastic Agents
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins
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RNA
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DNA
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Cisplatin