Despite a frequent effective therapeutic response in the first months of administration of targeted therapeutics the patients with an ALK rearrangement relapse or progress, essentially due to the emergence of mutations in ALK . Many different ALK mutations occur and can be detected by NGS analysis with free circulating tumor DNA. The detection of these mutations leads to changes in the targeted therapeutics. It is important to note that depending on the treatment used to target an ALK rearrangement, the resistance mutations that emerge on the ALK gene can be different . For example, the L1196M mutation often occurs after treatment with crizotinib, G1202R after ceritinib or alectinib, F1174C after ceretinib and I1171T/N/S after alectinib treatment .