In cases without the C797S mutation, although loss of T790M was reported as specific resistant mechanism to third-generation EGFR–TKIs, bypass pathway activation, such as c-MET activation or small-cell lung cancer (SCLC) transformation, in resistant tumours is thought to be the mechanism of resistance similar to that known in first-generation EGFR–TKIs33, 34, 35, 36, 37, 38, 39. Here, EGFR is linked to neoplasm.