Prediction of clinical outcome of fluoropyrimidine-based chemotherapy for gastric cancer patients, in terms of the 5-fluorouracil metabolic pathway.
Fluoropyrimidines are widely used in chemotherapy regimens for metastatic gastric cancer. Interindividual variation in the enzyme activity of the 5-fluorouracil (FU) metabolic pathway can affect the extent of 5-FU metabolism and affect the efficacy of 5-FU based chemotherapy. In this review, the role of the genetic factors affecting the therapeutic efficacy of fluoropyrimidines is discussed, with a special emphasis on enzymes involved in the 5-FU metabolic pathway. The gene expressions of thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, and orotate phosphoribosyltransferase are discussed in relation to the efficacy of fluoropyrimidine treatment for metastatic gastric cancer. These candidate genes, along with others yet to be identified, could allow accurate prediction of the clinical outcome in patients receiving fluoropyrimidine-based chemotherapy in the future. Well-designed and large prospective studies, which include relevant pharmacogenetic parameters, are needed to confirm the values required to predict clinical outcome.
Ichikawa
Wataru
W
Department of General and Digestive Surgery, Saitama Medical School, 38 Moro-Hongo, Moroyama, Iruma-gun, Saitama, 350-0495, Japan.
D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000627:therapeutic use; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000502:physiology; D005472:Fluorouracil / Q000378:metabolism* / Q000627:therapeutic use*; D005544:Forecasting; D006801:Humans; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000502:physiology; D009962:Orotate Phosphoribosyltransferase / Q000502:physiology; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000502:physiology; D011743:Pyrimidines / Q000378:metabolism / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D013939:Thymidine Phosphorylase / Q000502:physiology; D013940:Thymidylate Synthase / Q000235:genetics / Q000502:physiology; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D009097:Multienzyme Complexes; D011743:Pyrimidines; C027157:uridine 5'-monophosphate synthase; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D013939:Thymidine Phosphorylase; D009964:Orotidine-5'-Phosphate Decarboxylase; D005472:Fluorouracil