Publication in Thoracic Oncology

J Thorac Oncol. 2016 Aug 6. pii: S1556-0864(16)30706-7. doi: 10.1016/j.jtho.2016.07.027. [Epub ahead of print]

Expanded CTCs from a Patient with ALK Positive Lung Cancer Present EML4-ALK Rearrangement along with Resistance Mutation and Enable Drug Sensitivity Testing: A Case Study.

Zhang Z, Shiratsuchi H, Palanisamy N, Nagrath S, Ramnath N

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. The presented study identified EML4-ALK gene rearrangement in expanded CTCs from one ALK positive lung adenocarcinoma patient. At the time of radiographic progression, CTCs obtained from the patient revealed a drug resistance mutation, L1196M on the ALK gene. CTCs were expanded ex-vivo and drug sensitivity testing was performed using 2 ALK inhibitors, crizotinib and ceritinib. The half maximal inhibitory concentration (IC50) of ceritinib was 1664 nM compared with crizotinib, 2268 nM showing that ceritinib was a more potent ALK inhibitor. We demonstrate 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.

Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

PMID:

27507192

DOI:

10.1016/j.jtho.2016.07.027