Acquired resistance to ALK inhibitors on the other hand can be categorized into 2 subgroups, on-target and off-target mechanisms.7 To date, 96 decisive on-target resistance mutations have been described in NSCLC, the entity in which ALK inhibitors are administered most frequently in clinical routine.7 Alterations in bypass signaling pathways indirectly affecting the ALK gene functionality represent the essential mechanism for the development of off-target resistance. This evidence concerns the gene ALK and non-small cell lung carcinoma.