The acquisition of TKI resistance other than by secondary mutations has been reported in oncogene-driven lung cancers, such as crizotinib resistance mediated by amplification of the ALK fusion gene in NSCLC16, gefitinib (an epidermal growth factor receptor[EGFR] TKI) resistance mediated by activation of a bypass pathway through MET amplification or activation in EGFR-positive NSCLC17, 18, or ceritinib resistance mediated by the over-expression of ABCB1 in ALK-rearranged NSCLC19. This evidence concerns the gene ALK and lung cancer.