Schematic representation of main EGFR-TKIs resistance mechanisms.

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Presentation transcript:

Schematic representation of main EGFR-TKIs resistance mechanisms. 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. Floriana Morgillo et al. ESMO Open 2016;1:e000060 Copyright © European Society for Medical Oncology. All rights reserved.