An overview of the recent progress in irinotecan pharmacogenetics.
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.
Fujiwara
Yutaka
Y
Medical Oncology/Hematology, Department of Medicine, Kobe University Hospital & Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. yufujiwa@med.kobe-u.ac.jp
Minami
Hironobu
H
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000633:toxicity*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D043182:Carboxylesterase / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D018900:Dinucleotide Repeats; D064420:Drug-Related Side Effects and Adverse Reactions / Q000201:enzymology / Q000235:genetics; D005787:Gene Frequency; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D000077146:Irinotecan; D008954:Models, Biological; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011355:Prodrugs / Q000493:pharmacokinetics* / Q000633:toxicity*; D000099148:UGT1A1 Enzyme
D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D002166:Camptothecin; D043182:Carboxylesterase; D051544:Cytochrome P-450 CYP3A; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D011355:Prodrugs; D000099148:UGT1A1 Enzyme; C510163:CYP3A4 protein, human; C517204:CES2 protein, human