Can dihydropyrimidine dehydrogenase impact 5-fluorouracil-based treatment?
More than 80% of an administered 5-fluorouracil (5-FU) dose is degraded by dihydropyrimidine dehydrogenase (DPD), making it an important regulator of this commonly used anticancer agent. The high variation in population DPD activity, association with 5-FU activity, and development of DPD inhibitors have all contributed to the current focus on this enzyme. This review details the impact of DPD on 5-FU pharmacology, catalogues recent information on DPD mutations, evaluates the case for tumour DPD as a source of 5-FU resistance and introduces the clinical case for DPD inhibitors as a mechanism for the use of oral fluoropyrimidine therapies.
Milano
G
G
Laboratoire d'Oncopharmacologie, Centre Antoine-Lacassagne, Nice, France.
McLeod
H L
HL
D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use*; D002940:Circadian Rhythm; D042943:Dihydrouracil Dehydrogenase (NADP); D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil