The efficacy of 5-fluorouracil (5FU)-based therapy, which remains the cornerstone of gastrointestinal cancer treatment, depends upon the expression of enzymes involved in pyrimidine metabolism, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyltransferase (OPRT).
Thymidylate synthase (TS) gene polymorphisms such as tandem repeat (TR) polymorphisms and single-nucleotide polymorphisms (SNPs) affect transcriptional efficiency of the TS gene and may be prognostic markers for fluoropyrimidine-based therapy in various gastrointestinal cancers.
The cell-free mRNA transcripts in malignant effusions were highly detectable and cell-free TS mRNA in gastrointestinal cancer patients were strongly associated with the sensitivity of primary cancer cells to 5-FU in vitro.
Thymidylate synthase (TS), Dihydropyrimidine dehydrogenase (DPD) and Thymidine Phosphorylase (TP) gene expressions are reported to be predictive markers for 5-fluorouracil (5-FU) sensitivity in gastrointestinal cancer.
Patients with gastrointestinal cancers that express high TS levels have a poor prognosis with regard to fluoropyrimidine-based palliative chemotherapy or complete primary tumour resection.
Discrepancies between the gene expression, protein expression, and enzymatic activity of thymidylate synthase and dihydropyrimidine dehydrogenase in human gastrointestinal cancers and adjacent normal mucosa.
These results suggest a link between MTHFR genotype and the folate pool in gastrointestinal cancer, leading to the association of MTHFR genotype with TS inhibition rate upon 5-FU exposure.
We investigated the polymorphism on the repeat length of the TS gene and its relation to the number of 5-fluoro-dUMP (FdUMP) binding sites in human gastrointestinal cancers.