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.
Zhang Z, Shiratsuchi H, Palanisamy N, Nagrath S, and Ramnath N. 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. J Thorac Oncol 2017; 12(2):397-402.
J Thorac Oncol
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.
Medical Subject Headings
Adenocarcinoma; Adult; Anaplastic Lymphoma Kinase; Crizotinib; Drug Resistance, Neoplasm; Gene Rearrangement; Humans; Lung Neoplasms; Male; Mutation; Neoplasm Staging; Neoplastic Cells, Circulating; Oncogene Proteins, Fusion; Prognosis; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Receptor Protein-Tyrosine Kinases