EGFR and lung carcinoma: Secondary mutations in the EGFR driver gene are a primary cause of resistance to EGFR-TKIs 2, 3; in addition, other mutations including BRAF, PIK3CA, HER2 or c-MET amplifications, which were independent of EGFR pathway, account for 5-20% in EGFR-TKIs resistant lung cancer 37.