Abstract
Recent developments in a number of molecular profiling technologies, including genomic/genetic testing, proteomic profiling and metabolomic analysis have allowed the development of 'personalized medicine'. Irinotecan is one of the models for personalized medicine based on pharmacogenetics, and a number of clinical studies have revealed significant associations between UGT1A1*28 and irinotecan toxicity. Based on this cumulative evidence, the US FDA and pharmaceutical companies revised the irinotecan label in June 2005. However, a recommended strategy for irinotecan-dose adjustments based on individual genetic factors has not yet been fully established. This article provides an overview of recent progress in irinotecan pharmacogenetics and discusses the clinical significance of the UGT1A1 genotype/haplotype with regard to severe irinotecan toxicity.
MeSH terms
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Alleles
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Antineoplastic Agents / pharmacokinetics*
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Antineoplastic Agents / toxicity*
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Camptothecin / analogs & derivatives*
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Camptothecin / pharmacokinetics
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Camptothecin / toxicity
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Carboxylesterase / genetics
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Carboxylesterase / metabolism
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Cytochrome P-450 CYP3A / genetics
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Cytochrome P-450 CYP3A / metabolism
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Dinucleotide Repeats
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Drug-Related Side Effects and Adverse Reactions / enzymology
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Drug-Related Side Effects and Adverse Reactions / genetics
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Gene Frequency
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Glucuronosyltransferase / genetics
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Glucuronosyltransferase / metabolism
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Haplotypes
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Homozygote
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Humans
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Irinotecan
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Models, Biological
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Pharmacogenetics
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Polymorphism, Genetic
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Prodrugs / pharmacokinetics*
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Prodrugs / toxicity*
Substances
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ATP-Binding Cassette Transporters
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Antineoplastic Agents
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Prodrugs
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Irinotecan
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Cytochrome P-450 CYP3A
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CYP3A4 protein, human
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UGT1A1 enzyme
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Glucuronosyltransferase
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CES2 protein, human
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Carboxylesterase
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Camptothecin