UFT: mechanism of drug action.
The mechanism of action of fluorouracil (5-FU) and the oral fluoropyrimidines and the importance of biochemical modulation and inhibition of dihydropyrimidine dehydrogenase for oral application of the prodrugs of 5-FU are discussed. The regulation of thymidylate synthase, as well as its roles as a target for antineoplastic activity and in drug resistance, are also mentioned. The more downstream events of 5-FU action and their implication in 5-FU resistance, with the possible involvement of the Fas/FasL system and the proteins associated with apoptosis regulation, are highlighted. Also discussed is the suggestion that the oral 5-FU prodrug tegafur and uracil (UFT) and its metabolites function as an angiogenesis inhibitor.
Köhne
C H
CH
Department of Hematology/Oncology, University of Rostock, Germany. Henning.koehne@med.uni-rostock.de
Peters
G J
GJ
D000284:Administration, Oral; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017209:Apoptosis / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000493:pharmacokinetics*; D006801:Humans; D005641:Tegafur / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000187:drug effects / Q000378:metabolism; D014498:Uracil / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase; D005472:Fluorouracil