Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyltransferase (OPRT) have been reported to be predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy. mRNA expression of TS, DPD, TP, and OPRT were quantified by reverse-transcriptase polymerase chain reaction after harvesting cancer cells from 93 paraffin-embedded specimens of gastric cancer through laser capture microdissection.
Thymidylate synthase and thymidine phosphorylase gene expression as predictive parameters for the efficacy of 5-fluorouracil-based adjuvant chemotherapy for gastric cancer.
Thymidylate synthetase is the major target of 5-fluorouracil (5-FU), which is widely used for the treatment of gastric cancer (GC) and colorectal cancer (CRC).
Thymidylate synthase is associated with risk of colorectal cancer but not with gastric cancer; however, heterozygous SL (2R/3R) polymorphism is associated with risk of gastric cancer; moreover, the 5' tandem repeat polymorphism of thymidylate synthase gene was an independent predictor of the clinical treatment.
A novel intraperitoneal therapy for gastric cancer with DFP-10825, a unique RNAi therapeutic targeting thymidylate synthase, in a peritoneally disseminated xenograft model.
A randomized study was conducted to investigate schedule-dependent thymidylate synthase (TS) inhibition by 5-FU in 16 patients with gastric cancer who underwent surgical resection.
Changes in intratumoral thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) mRNA expression in colorectal and gastric cancer during continuous tegafur infusion.
ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy.
Expression of thymidylate synthase determines the response of gastric cancer patients undergoing gastrectomy to 5-fluorouracil-based adjuvant chemotherapy.
In both gastric and colon cancers, thymidylate synthase and orotate phosphoribosyltransferase mRNA expressions were higher (p < 0.0001, p <0.0001 respectively in gastric cancer and P = 0.0002, p < 0.0001 respectively in colon cancer) and dihydropyrimidine dehydrogenase mRNA expressions were lower in cancer cells than in cancerous stroma (P = 0.0136 in gastric cancer and p < 0.0001 in colon cancer).
In conclusion, the TYMS polymorphisms, especially the TS3'UTR polymorphism, are associated with GC risk, especially the non-cardiac gastric cancer, and the TSER 2R and TS3'UTR 6 bp alleles may jointly play a role in the etiology of GC in the southern Chinese population.
In conclusion, the detection of DPD and/or TS mRNA expression can be used to predict the response to S-1-based chemotherapy, drug resistance, and prognosis in AGC patients as well as to help guide the individualized treatment of gastric cancer.
Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker.
Our results suggested that intratumoral TS expression is an independent prognostic factor in patients with gastric cancer who received postoperative adjuvant chemotherapy with S-1.
Polymorphisms of the TS gene affect the expression of the gene, which in turn may result in differences in the outcome of cancer chemotherapy and the progression of gastric cancer.