EML4-ALK translocation identification in RNA exosomal cargo ( ExoALK ) in NSCLC patients: a novel role for liquid biopsy

Lung cancer treatment landscape has completely changed in the last decade. The introduction of druggable targets in the therapeutic scenario gave the opportunity to significantly improve the outcomes in the most lethal malignant disease. EML4-ALK translocation represents a story of success in drug development. The discovery of the aberration in tumors of patients with lung cancer in 2007 (1) soon translated into a rapid approval of the first ALK tyrosine kinase inhibitor (TKI), crizotinib (2), and the subsequent early arrival of second and third generation TKIs, all happening in roughly a decade. The current standard for the identification of the target necessarily implies identification of rearrangement in the tumor tissue either by FISH or immunohistochemistry. Unfortunately, despite the efforts, a big number of non-small cell lung cancer (NSCLC) patients have no tissue available for determination. The isolation of ctDNA is a novel approach, but still not validated for EML4-ALK translocation (3,4). Exosomes, new members of the liquid biopsy family, carrying genetic material represent an important tool for biomarkers discovery (5). Our group has identified, for the first time, EML4-ALK translocation in exosomes (ExoALK), using a next generation sequencing technique