Lung cancer is the leading cause of cancer death worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. The discovery that the EML4–ALK fusion protein kinase is a potent oncogenic driver in 3–7% of patients with NSCLC led to the development of the ALK inhibitor crizotinib. This agent and an accompanying companion diagnostic test were granted FDA approval for the detection of ALK-rearrangements. The test is performed on tumour biopsies or fine-needle aspirates, but is hampered by the lack of available tumour tissue.
A group led by Françoise Farace has evaluated whether circulating tumour cells (CTCs) might represent a noninvasive source of tumour material in NSCLC. Researchers isolated CTCs from 32 patients with metastatic NSCLC, 18 of whom had ALK-positive tumours. Farace explains: “Because cell number is an essential criterion to exploit CTCs ... we focused on the development of a fluorescence in situ hybridization (FISH) method on filters (Filter Adapted-FISH, FA-FISH) that takes into account the very fragile nature of CTCs and allows high cell recovery.”
ALK rearrangements were found in CTCs from all the patients with ALK-positive tumours. These CTCs had a unique ALK rearrangement and a mesenchymal phenotype, in contrast to the heterogeneous epithelial/mesenchymal phenotypes in the patient's tumours. Farace concludes, “ALK-rearranged CTCs could result from a clonal selection process of tumour cells displaying migratory and invasive properties, and possibly a higher metastatic potential. CTCs could represent a unique compartment to identify tumour clones that should be targeted by personalized treatments, as well as biomarkers that are more relevant for treatment prediction.”
ORIGINAL RESEARCH PAPER
Pailler, E. et al. Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non–small-cell lung cancer. J. Clin. Oncol. doi:10.1200/JCO.2012.44.5932
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Marchesi, V. ALK status of NSCLC reflected in CTCs. Nat Rev Clin Oncol 10, 366 (2013). https://doi.org/10.1038/nrclinonc.2013.89
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DOI: https://doi.org/10.1038/nrclinonc.2013.89
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