Recently, the third generation ALK-TKI lorlatinib was approved to treat refractory ALK-positive NSCLC patients11; however, as complete response to any of the classes of ALK-TKIs is rare, almost all patients with ALK-rearranged NSCLC inevitably acquire resistance to ALK-TKIs, including alectinib and brigatinib. The gene discussed is ALK; the disease is non-small cell lung carcinoma.