Identification of thymidylate synthase as a potential therapeutic target for lung cancer

摘要: Thymidylate synthase (TS) is an essential enzyme that catalyses the transfer of a methyl group from methylenetetrahydrofolate to dUMP generate dTMP (Carreras and Santi, 1995). The subsequent phosphorylation dTTP provides direct precursor for DNA synthesis. level TS expression increased in highly proliferative cells, abundance broad range tumours associated with poor treatment response prognosis (Costi et al, 2005). Transfection nontransformed cells vector has also been found confer transformed-like behaviour, suggesting itself potential oncoprotein (Rahman 2004). These findings have led being considered as molecular target cancer therapy. To date, antiproliferative effect inhibition examined mostly use drugs such 5-fluorouracil its active metabolite 5-fluoro-dUMP, former which used chemotherapy. Although studies antisense oligodeoxynucleotides shown depletion results growth human tumour (Ferguson 1999; Lin 2001; Flynn 2006), underlying mechanism specific remained largely unknown. Lung one most common forms worldwide. Advanced lung treated by combination chemotherapy, although further improvement therapy warranted. High levels TS-targeting agents individuals advanced (Oguri 2005; Kubota 2009; Ozasa 2009), biological relevance be well established. We now abrogated both activity application RNA interference (RNAi). With this approach, we investigated precise role chemotherapeutic these cells. Our provide basis development TS-targeted patients.