Schematic representation of main EGFR-TKIs resistance mechanisms. Resistance to EGFR-TKIs can occur through different mechanisms either intrinsic or acquired. Known mechanisms are secondary resistance mutations occurring in the ATP-binding domain (such as T790M and C797S), mutation or amplification of bypass signallings (such as AXL, Hh, ERBb2, CRIPTO, etc), activating mutations in the downstream pathways (PI3K, AKT, MEK, RAF), low levels of mRNA or polymorphisms of the pro-apoptotic protein BIM, induction of a transcription programme for EMT and phenotypical changes, or induction of elevated tumour PD-L1 levels. EGFR, epidermal growth factor receptor; EMT, epithelial-to-mesenchymal transition; mRNA, messenger RNA; PD-1, programmed death receptor-1; PD-L1, programmed death ligand-1; TKI, tyrosine kinase inhibitor.
Morgillo, F., Della Corte, C. M., Fasano, M., & Ciardiello, F.(2016).
Mechanisms of resistance to EGFR-targeted drugs: lung cancer.
Accessed May 22, 2017.https://doi.org/10.1136/esmoopen-2016-000060.