Emerging role of thymidylate synthase for the pharmacogenomic selection of patients with thoracic cancer.

摘要

The use of antifolate drags, and particularly of pemetrexed, is emerging as a relevam therapeutic strategy for the treatment of some specific thoracic cancers.Pemetrexed is a novel multitargeted antifolate which has been shown in vitro to inhibii at least three different enzymes in the folate pathway: thymidylate synthase (TS), dihydro-folate reductase (DHFR) and glycinarm'de ribonucleotide formyl transferase (GARFT of which TS is its main target [1]. These enzymes are involved in the synthesis of nucleo-tides and interference with their function wili ultimately hinder the synthesis of RNA anc DNA. Pre-clinical studies have demonstratec the cytotoxic activity of this agent in a broac range of tumor types including non-small eel lung cancer (NSCLC). In vitro studies indicated that tumor cell lines expressing higr levels of TS or DHFR have reduced sensitivity to pemetrexed, suggesting that increasec expression levels might correlate with reduced clinical efficacy [2],