期刊
JOURNAL OF THORACIC ONCOLOGY
卷 12, 期 2, 页码 397-402出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtho.2016.07.027
关键词
EML4-ALK; Expanded CTCs; NSCLC; L1196M; Liquid biopsy
资金
- University of Michigan Cancer Center
- National Institutes of Health
- United States Department of Defense
The emergence of liquid biopsy using circulating tumor cells (CTCs) as a resource to identify genomic alterations in cancer presents new opportunities for diagnosis, therapy, and surveillance. We identified EML4-ALK gene rearrangement in expanded CTCs from a patient with ALK-positive lung adenocarcinoma. At the time of radiographic progression, CTCs obtained from the patient revealed a drug resistance mutation (i.e., L1196M on the ALK gene). CTCs were expanded ex vivo and drug sensitivity testing was performed using two ALK inhibitors, crizotinib and ceritinib. The half maximal inhibitory concentration of ceritinib was 1664 nM compared with crizotinib (2268 nM), showing that ceritinib was a more potent ALK inhibitor. We show that it is feasible to detect serial genetic alterations in expanded CTCs and perform in vitro drug screening. These findings support the clinical utility of CTCs not only for diagnosis, but also a potential tool for drug sensitivity testing in distinct subsets of lung cancer and for personalized precision medicine. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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