Dihydropyrimidine dehydrogenase polymorphisms and fluoropyrimidine toxicity: Ready for routine clinical application within personalized medicine?

被引：21

作者：

Del Re M. ^{[1
]}

Di Paolo A. ^{[1
]}

van Schaik R.H. ^{[2
]}

Bocci G. ^{[1
]}

Simi P. ^{[3
]}

Falcone A. ^{[4
]}

Danesi R. ^{[1
]}

机构：

[1] Division of Pharmacology, Department of Internal Medicine, University of Pisa, 56126 Pisa, 55, Via Roma

[2] Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam

[3] Unit of Cytogenetics and Molecular Genetics, University Hospital, Pisa

[4] Division of Oncology, Department of Oncology, Transplants and Advanced Technologies in Medicine, University of Pisa, Pisa

来源：

EPMA Journal | 2010年 / 1卷 / 3期

关键词：

DPD; Fluoropyrimidines; Personalized medicine; Polymorphisms; Toxicity;

D O I：

10.1007/s13167-010-0041-2

中图分类号：

学科分类号：

摘要：

Fluoropyrimidines, including 5-fluorouracil (5-FU), are widely used in the treatment of solid tumors and remain the backbone of many combination regimens. Despite their clinical benefit, fluoropyrimidines are associated with gastrointestinal and hematologic toxicities, which often lead to treatment discontinuation. 5-FU undergoes complex metabolism, dihydropyrimidine dehydrogenase (DPD) being the rate-limiting enzyme of inactivation of 5-FU and its prodrugs. Several studies have demonstrated significant associations between severe toxicities by fluoropyrimidines and germline polymorphisms of DPD gene. To date, more than 30 SNPs and deletions have been identified within DPD, the majority of these variants having no functional consequences on enzymatic activity. However, the identification of deficient DPD genotypes may help identify poor-metabolizer patients at risk of developing potentially life-threatening toxicities after standard doses of fluoropyrimidines. © 2010 European Association for Predictive, Preventive and Personalised Medicine.

引用

页码：495 / 502

页数：7

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