EGFR-independent mechanisms include bypass pathway or downstream activation by amplification of MET (8, 23), CRKL (24), HER2 (25), SMO (26), ERK (27) and KRAS (28)et al. Other altered molecular mechanisms involved in EGFR blockade resistance are transformation to small-cell lung cancer, epithelial-mesenchymal transition (10, 29–31), and the activation of immune system and other immunosuppressive factors, such as PD-L1 (32). The gene discussed is CRKL; the disease is small cell lung carcinoma.