1. Expanded Circulating Tumor Cells from a Patient with ALK-Positive Lung Cancer Present with EML4-ALK Rearrangement Along with Resistance Mutation and Enable Drug Sensitivity Testing: A Case Study.
- Author
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Zhang Z, Shiratsuchi H, Palanisamy N, Nagrath S, and Ramnath N
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma genetics, Adenocarcinoma pathology, Adult, Anaplastic Lymphoma Kinase, Crizotinib, Humans, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Male, Neoplasm Staging, Neoplastic Cells, Circulating drug effects, Neoplastic Cells, Circulating metabolism, Prognosis, Protein Kinase Inhibitors therapeutic use, Drug Resistance, Neoplasm genetics, Gene Rearrangement, Lung Neoplasms pathology, Mutation, Neoplastic Cells, Circulating pathology, Oncogene Proteins, Fusion genetics, Pyrazoles therapeutic use, Pyridines therapeutic use, Receptor Protein-Tyrosine Kinases genetics
- Abstract
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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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