title: 5-Fluorouracil pharmacogenomics: still rocking after all these years?
abstract: The 5-fluorouracil (5-FU) metabolic pathway is mainly dependent on the activity of several intracellular enzymes. Among them, four in particular; thymidylate synthase, methylenetetrahydrofolate reductase, dihydropyrimidine dehydrogenase and thymidine phosphorylase are considered the key points in determining sensitivity or resistance to this drug. These enzymes are needed to metabolize the drug in its active form (thymidylate phosphorylase) or to drop the concentration of the active drug in the cell (dihydropyrimidine dehydrogenase) or both (thymidylate synthase and methylenetetrahydrofolate reductase). Several different studies have tried to investigate the relationship between the presence of mutations in these enzymes and a reduced/improved activity of treatment based on 5-FU or its derivatives. In this article, we will focus on the often contradictory results of these studies.
authors.affiliation: Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona, Italy. marioscartozzi@gmail.com
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.forename: Elena
authors.initials: E
authors.lastname: Maccaroni
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giampieri
authors.forename: Mirco
authors.initials: M
authors.lastname: Pistelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bittoni
authors.forename: Michela
authors.initials: M
authors.lastname: Del Prete
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism; D005472:Fluorouracil / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D013939:Thymidine Phosphorylase / Q000235:genetics* / Q000378:metabolism; D013940:Thymidylate Synthase / Q000235:genetics* / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase; D013939:Thymidine Phosphorylase; D005472:Fluorouracil