AKT1 and neoplasm: The second category of resistance is associated with re-activation of the two main EGFR downstream signaling pathways PI3K-AKT and MEK/ERK, such as MET was found to promote resistance by reactivating both PI3K-AKT and MEK/ERK signaling despite the inhibition of EGFR (8); In addition, tumor resistance undergoes cell/tumor phenotypic/histological changes, such as epithelial-to-mesenchymal transition (EMT) histological transformation and development toward small-cell lung cancer (SCLC) (9–11).