Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona, Italy.
Pharmacogenomics. 2011 Feb;12(2):251-65. doi: 10.2217/pgs.10.167.
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.
5-氟尿嘧啶（5-FU）的代谢途径主要依赖于几种细胞内酶的活性。其中，有四种特别重要的酶：胸苷酸合成酶、亚甲基四氢叶酸还原酶、二氢嘧啶脱氢酶和胸苷磷酸化酶，被认为是决定对该药物敏感性或耐药性的关键因素。这些酶是将药物代谢为其活性形式（胸苷磷酸化酶）所必需的，或者是降低细胞内活性药物的浓度（二氢嘧啶脱氢酶），或者两者兼而有之（胸苷酸合成酶和亚甲基四氢叶酸还原酶）。多项不同的研究试图探究这些酶的突变与基于 5-FU 或其衍生物的治疗效果降低/提高之间的关系。在本文中，我们将重点关注这些研究结果中经常存在的矛盾之处。
