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.”