**3.3 ALK translocations**

ALK gene mutations, copy number changes, or fusion with other genes have oncogenic effects. Similar to EGFR mutations, translocations of ALK are predictive of response to Tyrosine Kinase Inhibitors (TKIs) [54]. ALK testing is mostly recommended for non-squamous cell lung cancers lacking EGFR mutations. The fusion between ALK and EML4 (echinoderm microtubule-associated protein-like 4) produces molecular variants with diverse biological functions and affects various signaling pathways [55, 56]. The incidence of cerebral metastases in NSCLC with ALK mutations is high and ALK translocations of primary tumors and their brain metastases are often similar. Interestingly, the progress of brain metastases of tumors with ALK mutations slows down significantly when treated with targeted therapy: over 45% of patients with BM had overall survival rates of three years [57]. Because nearly 45% of patients with ALK-positive NSCLC have developed BM at death [58], cerebral seeding is an important clinical challenge for developing strategies for personalized care in NSCLC [59].
