EGFR and small cell lung carcinoma: For example, acquired resistance mechanisms to EGFR-TKIs include on-target resistance and off-target resistance, the former of which may show a second-site mutation in the EGFR kinase domain, preventing its binding with EGFR-TKIs, and the latter of which may result from alterations of the downstream components of the EGFR pathway, activation of alternative signaling pathways that bypass the primary drug targets, including MET amplification, or transition to another cell lineage, e.g., epithelial-to-mesenchymal transition (EMT) and SCLC transformation (2).