Regulation of human dihydropyrimidine dehydrogenase: implications in the pharmacogenetics of 5-FU-based chemotherapy.
Dihydropyrimidine dehydrogenase is the enzyme that is critical for the efficacy and toxicity of the anticancer reagent 5-fluorouracil. It has been demonstrated that the regulation of the dihydropyrimidine dehydrogenase gene has an important role in the determination of the enzyme activity of dihydropyrimidine dehydrogenase. The regulation of the gene expression is thus discussed from two aspects: normal regulation by specificity proteins, and the epigenetic regulation by promoter methylation. The influence of the polymorphism on dihydropyrimidine dehydrogenase enzyme activity and other factors that have been suggested to be involved in dihydropyrimidine dehydrogenase regulation are also discussed.
Zhang
Xue
X
University of Alabama, Department of Pharmacology and Toxicology, Birmingham, AL 35294, USA.
Diasio
Robert B
RB
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005472:Fluorouracil / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000502:physiology
D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil