Document Detail


Role of pharmacogenetics in irinotecan therapy.
MedLine Citation:
PMID:  16343744     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the treatment of advanced colorectal cancer, irinotecan has become one of the most important drugs, despite its sometimes unpredictable adverse effects. To understand why some patients experience severe adverse effects (diarrhea and neutropenia), while others do not, the metabolic pathways of this drug have to be unraveled in detail. Individual variation in expression of several phase I and phase II metabolizing enzymes and ABC-transporters involved in irinotecan metabolism and excretion, at least partly explains the observed pharmacokinetic interpatient variability. Although the difference in expression-level of these proteins to a certain amount is explained by physiologic and environmental factors, the presence of specific genetic determinants also does influence their expression and function. In this review, the role of genetic polymorphisms in the main enzyme-systems (carboxylesterase, cytochrome P450 3A, and uridine diphosphate-glucuronosyltransferase) and ABC-transporters (ABCB1, ABCC2, and ABCG2) involved in irinotecan metabolism, are discussed. Since at this moment the field of pharmacogenetics and pharmacogenomics is rapidly expanding and simultaneously more rapid and cost-effective screening methods are emerging, a wealth of future data is expected to enrich our knowledge of the genetic basis of irinotecan metabolism. Eventually, this may help to truly individualize the dosing of this (and other) anti-cancer agent(s), using a personal genetic profile of the most relevant enzymes for every patient.
Authors:
Floris A de Jong; Maja J A de Jonge; Jaap Verweij; Ron H J Mathijssen
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Publication Detail:
Type:  Journal Article; Review     Date:  2005-12-15
Journal Detail:
Title:  Cancer letters     Volume:  234     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-10     Completed Date:  2006-05-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  90-106     Citation Subset:  IM    
Affiliation:
Department of Medical Oncology, Daniel den Hoed Cancer Center, Erasmus University Medical Center Rotterdam, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands. f.a.dejong@erasmusmc.nl
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism
Animals
Antineoplastic Agents, Phytogenic / therapeutic use*
Camptothecin / analogs & derivatives*,  therapeutic use
Forecasting
Humans
Neoplasms / drug therapy*,  genetics
Pharmacogenetics*
Polymorphism, Genetic / genetics
Chemical
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Antineoplastic Agents, Phytogenic; 100286-90-6/irinotecan; 7689-03-4/Camptothecin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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