[A brief overview of a lung cancer biomarker: thymidylate synthase]

Abstract

Thymidylate synthase (TS) is an enzyme, which catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5.10-methylenetetrahydrofolate as a cofactor. For this reason, TS has been widely investigated and is one of the best-known drug targets in the anticancer area. Antimetabolites have been developed to target TS and among them, pemetrexed is now considered as part of the standard treatment for lung cancer and mesothelioma. Intratumoral expression of TS mRNA has been shown to be associated with prognosis and with the response to 5-FU therapy in patients with breast, colorectal, head and neck cancer types. Recent findings suggest that TS might be a biomarker for NSCLC treated with pemetrexed, as lower response rates in squamous cell carcinoma and small cell carcinoma may be due to a higher expression of TS. Specific validation for this use as a biomarker is awaited. All these recent findings suggest that TS could be a useful predictive marker of the treatment efficacy of antifolate drugs and indicate that both Real-Time PCR and immuno-histochemistry might be used to assess TS expression levels. This may help in defining the best therapeutic strategy.