MET amplification is the most common alternative pathway activation [81,82], but other mechanisms can also lead to acquired resistance to EGFR-TKIs, including the following: HER2 amplification [83]; HER3 overexpression (HER3 activation) [84]; KRAS, BRAF, and MAPK1 mutations [85,86]; ALK fusions; GFR3-TACC3, RET-ERC1, CCDC6-RET, NTRK1-TPM3, NCOA4-RET, GOPC-ROS1, AGKBF and ESYT2-BF fusions [87,88]; the transformation of NSCLC into SCLC [82], adenocarcinoma into squamous cell carcinoma [89], and EMT [90]. The gene discussed is ERBB3; the disease is non-small cell lung carcinoma.