Role of cytochrome P450 activity in the fate of anticancer agents and in drug resistance: focus on tamoxifen, paclitaxel and imatinib metabolism
Détails
ID Serval
serval:BIB_91FEB5E4A9DC
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Role of cytochrome P450 activity in the fate of anticancer agents and in drug resistance: focus on tamoxifen, paclitaxel and imatinib metabolism
Périodique
Clinical Pharmacokinetics
ISSN
0312-5963 (Print)
Statut éditorial
Publié
Date de publication
2005
Volume
44
Numéro
4
Pages
349-66
Notes
Journal Article
Review
Review
Résumé
Although activity of cytochrome P450 isoenzymes (CYPs) plays a major role in the fate of anticancer agents in patients, there are relatively few clinical studies that evaluate drug metabolism with therapeutic outcome. Nevertheless, many clinical reports in various non-oncology fields have shown the dramatic importance of CYP activity in therapeutic efficacy, safety and interindividual variability of drug pharmacokinetics. Moreover, variability of drug metabolism in the liver as well as in cancer cells must also be considered as a potential factor mediating cancer resistance.This review underlines the role of drug metabolism mediated by CYPs in pharmacokinetic variability, drug resistance and safety. As examples, biotransformation pathways of tamoxifen, paclitaxel and imatinib are reviewed.This review emphasises the key role of therapeutic drug monitoring as a complementary tool of investigation to in vitro data. For instance, pharmacokinetic data of anticancer agents have not often been published within subpopulations of patients who show ultra-rapid, extensive or poor metabolism (e.g. due to CYP2D6 and CYP2C19 genotypes).Besides kinetic variability in the systemic circulation, induction of CYP activity may participate in creating drug resistance by speeding up the cancer agent degradation specifically in the target cells. For one cancer agent, various mechanisms of resistance are usually identified within different cell clones. This review also tries to emphasise that drug resistance mediated by CYP activity in cancer cells should be taken into consideration to a greater degree.The unequivocal identification of the metabolising enzymes involved in clinical conditions will eventually allow improvement and individualisation of anticancer agent therapy, i.e. drug dosage and selection. In addition, a more complete understanding of the metabolism of anticancer agents will assist in the prediction of drug-drug interactions, as anticancer agent combinations are becoming more prevalent.
Mots-clé
Antineoplastic Agents/adverse effects/*pharmacokinetics
Biotransformation
Cytochrome P-450 Enzyme System/genetics/*metabolism
Drug Interactions
Drug Monitoring
*Drug Resistance, Neoplasm
Humans
Isoenzymes/genetics/metabolism
Neoplasms/drug therapy/metabolism
Paclitaxel/adverse effects/pharmacokinetics
Piperazines/adverse effects/pharmacokinetics
Polymorphism, Genetic
Pyrimidines/adverse effects/pharmacokinetics
Tamoxifen/adverse effects/pharmacokinetics
Pubmed
Web of science
Création de la notice
25/01/2008 9:47
Dernière modification de la notice
20/08/2019 15:55