Thymidylate Synthase as a Determinant of Pemetrexed Sensitivity in Non-Small Cell Lung Cancer

摘要: Although a high level of thymidylate synthase (TS) expression in malignant tumours has been suggested to be related reduced sensitivity the antifolate drug pemetrexed, no direct evidence for such an association demonstrated non-small cell lung cancer (NSCLC). We have now investigated effect TS overexpression on pemetrexed NSCLC cells. established lines that stably overexpress and examined effects cytotoxicity both vitro xenograft models. further relation between tumour specimens from patients response by immunohistochemical analysis. The cells overexpressing antiproliferative was markedly compared with control inhibition DNA synthesis induction apoptosis were also greatly attenuated forced TS. Furthermore, formed TS-overexpressing nude mice resistant growth-inhibitory observed tumours. Finally, non-responding significantly higher than those responders, suggestive inverse correlation pemetrexed. A confers is thus potential predictive marker pemetrexed-based chemotherapy patients.