Publication in refereed journal
香港中文大学研究人员 ( 现职)
| 莫树锦教授 (肿瘤学系) |
全文
| 数位物件识别号 (DOI) http://dx.doi.org/10.1016/j.ccr.2009.11.022 |
引用次数
Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/493WOS source URL
其它资讯
摘要MET amplification activates ERBB3/PI3K/AKT signaling in EGFR mutant lung cancers and causes resistance to EGFR kinase inhibitors. We demonstrate that MET activation by its ligand, HGF, also induces drug resistance, but through GAB1 signaling. Using high-throughput FISH analyses in both cell lines and in patients with lung cancer, we identify subpopulations; of cells with MET amplification prior to drug exposure. Surprisingly, HGF accelerates the development of MET amplification both in vitro and in vivo. EGFR kinase inhibitor resistance, due to either MET amplification or autocrine HGF production, was cured in vivo by combined EGFR and MET inhibition. These findings highlight the potential to prospectively identify treatment naive, patients with EGFR-mutant lung cancer who will benefit from initial combination therapy.
着者Turke AB, Zejnullahu K, Wu YL, Song Y, Dias-Santagata D, Lifshits E, Toschi L, Rogers A, Mok T, Sequist L, Lindeman NI, Murphy C, Akhavanfard S, Yeap BY, Xiao Y, Capelletti M, Iafrate AJ, Lee C, Christensen JG, Engelman JA, Janne PA
期刊名称Cancer Cell
出版年份2010
月份1
日期19
卷号17
期次1
出版社Elsevier (Cell Press)
页次77 - 88
国际标準期刊号1535-6108
电子国际标準期刊号1878-3686
语言英式英语
Web of Science 学科类别Cell Biology; CELL BIOLOGY; Oncology; ONCOLOGY
