A few mechanisms of primary or acquired resistance have been identified, which include on-target EGFR-dependent mechanisms of resistance (e.g., exon 20 T790M and C797S mutations) and off-target EGFR-independent mechanisms (e.g., histologic transformation to small cell lung cancer, or acquisition of other driver alterations such as MET, HER2, p53, or PI3KCA amplification) [16,17,18,19,20,21,22,23,24,25]. This evidence concerns the gene EGFR and small cell lung carcinoma.