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ORIGINAL ARTICLE Genetic Determinants of Pemetrexed Responsiveness and Nonresponsiveness in Non-small Cell Lung Cancer Cells Ming-Fang Wu, MD, PhD,*† Yi-Min Hsiao, PhD,‡ Chuan-Fu Huang, MD, PhD,† Yu-Hsin Huang, MS,§ Wan-Jung Yang, BS,§ Hsiu-Wen Chan, MS,§ Jinghua Tsai Chang, PhD,*§ and Jiunn-Liang Ko, PhD*§ genes may serve as new biomarkers for predicting responsiveness to Background: Pemetrexed disodium (Alimta), LY231514, is an pemetrexed. antifolate that is able to simultaneously inhibit the synthesis of Key Words: Biomarker, Lung cancer, Lipocalin-2, nm23-H1. purines and pyrimidines. Pemetrexed has been approved for first- and second-line treatment in patients with non-small cell lung cancer (J Thorac Oncol. 2010;5: 1143–1151) (NSCLC). However, there is still a lack of clinical biomarkers for predicting the therapeutic response to pemetrexed. The aim of this study is to establish new biomarkers for pemetrexed treatment in emetrexed (Alimta), a new multitarget antifolate metab- NSCLC. Polite anticancer drug, is an inhibitor of thymidylate syn- Methods: Human NSCLC cell lines were exposed to pemetrexed. thase (TS), dihydrofolate reductase (DHFR), and glycinamide The antitumor effect was measured by growth inhibition with MTT ribonucleotide formyl transferase (GARFT) and has broad- assay and expression of cell cycle mediators with immunoblots. spectrum activity in multiple tumor types. Pemetrexed
Journal of Thoracic Oncology – Wolters Kluwer Health
Published: Aug 1, 2010
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