With the recognition that TS is an important therapeutic target, direct and specific inhibitors have been developed and are under intensive preclinical and clinical evaluation, primarily in patients with colorectal cancer, with demonstrable activity.
TS mRNA expression was shown to be significantly higher in the pulmonary metastases (mean TS/beta-actin ratio, 19.7; n = 7) as compared with the hepatic metastases (mean TS/beta-actin ratio, 4.7; n = 11) of colorectal cancer.
Results of other studies of adjuvant therapy in gastric cancer and colorectal cancer also indicated that TS expression within the tumor is predictive of response of 5-FU-based therapy.
Although the number of patients is relatively small, these results identify p53 status and TS gene expression as associated with response in disseminated colorectal cancer; independent studies are needed to confirm these findings and to provide information leading to a better understanding of the role of 5-FU-based chemotherapy in the treatment of colorectal cancer.
Immunohistochemical determination of p53 protein does not predict clinical response in advanced colorectal cancer with low thymidylate synthase expression receiving a bolus 5-fluorouracil-leucovorin combination.
Now we report on the use of RT-PCR techniques to see if that variant TS form could be present in human samples from patients who underwent surgery for primary colorectal cancer and been previously untreated and to try to find relationships between that hypothetical variant TS form and the 5-Fluorouracil treatment.
The enzyme thymidylate synthase (TS) is an important target of 5-fluorouracil (FUra) that is utilized for the treatment of disseminated colorectal cancer.
Our data suggest that genotyping patients for the thymidylate synthase polymorphism would be useful in identifying patients who are more likely to respond to capecitabine treatment for advanced colorectal cancer.
ZD9331, a highly specific TS inhibitor that dose not require polyglutamation for its activation, has shown activity in patients with refractory ovarian and colorectal cancer.
The aim of this study was to evaluate three molecular genetic markers - p53, DCC (deleted in colonic cancer) and thymidylate synthase - in both the primary colorectal tumour and the resected hepatic metastases, and to determine their correlation, if any, with survival in patients with resected hepatic metastases from colorectal cancer.
In this study, we investigated the TS genotype in 151 matched tumor and normal DNA samples isolated from colorectal cancer and adjacent normal tissues by PCR analysis.
Thymidylate synthase (TS) is the target enzyme for 5-fluorouracil (5-FU), and TS expression may determine clinical response and survival after therapy with 5-FU in colorectal cancer.
The result suggests that mRNA translation is responsible for the genotype-dependent difference of TS protein expression, as is consistent with our previous observation in colorectal cancer.
The aim of this study was to evaluate three potential molecular genetic markers of prognosis (p53, deleted in colorectal cancer gene, and thymidylate synthase) in Dukes Stage B and C low rectal tumors treated with adjuvant therapy and to determine whether they correlate with survival, local recurrence, or the pathologic response to adjuvant therapy (assessed by extent of tumor regression and tumor down-staging).
Polymorphism in the thymidylate synthase promoter enhancer region is not an efficacious marker for tumor sensitivity to 5-fluorouracil-based oral adjuvant chemotherapy in colorectal cancer.
Thymidylate synthase (TS) is an important target for chemotherapy and increased levels are associated with resistance to colorectal cancer chemotherapy.
In this study, we determined the prognostic value of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer patients treated with adjuvant 5-FU.
Real-time PCR was used to quantify expression levels of folate-associated genes including the reduced folate carrier (RFC-1), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH),and thymidylate synthase (TS) in tumor tissue and adjacent mucosa of patients with primary colorectal cancer (n=102).