Fig. 1.

Three different levels of drug resistance mechanisms in lung cancer. Drug resistance develops at three different levels: molecular, cellular, and pathological level. Molecular level mechanism includes secondary EGFR T790M and MET amplification after the relapse from EGFR-TKI therapy. Cellular level mechanism mainly involves CSC and EMT. Pathological level mechanism includes the ADC-to-SCC transition and ADC or SCC-to-SCLC transition. EGFR epidermal growth factor receptor, EGFR-TKI epidermal growth factor receptor-tyrosine kinase inhibitor, BRAF serine/threonine-protein kinase B-raf, HER2 receptor tyrosine-protein kinase erbB-2, PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, MET hepatocyte growth factor receptor, EMT epithelial-to-mesenchymal transition, CSC cell stem cell, ADC adenocarcinoma, SCC squamous cell carcinoma, SCLC small cell lung cancer