Dihydropyrimidine dehydrogenase polymorphisms and fluoropyrimidine toxicity: ready for routine clinical application within personalized medicine? View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-09

AUTHORS

Marzia Del Re, Antonello Di Paolo, Ron H. van Schaik, Guido Bocci, Paolo Simi, Alfredo Falcone, Romano Danesi

ABSTRACT

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. More... »

PAGES

495-502

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13167-010-0041-2

DOI

http://dx.doi.org/10.1007/s13167-010-0041-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1035526290

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23199091


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