Mechanisms of resistance to EGFR tyrosine kinase inhibitors

Since the discovery that inn small cell lung cancer (NSCLC) is driven by epidermal growth factor receptor (EGFR) mutations, the EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g., gefitinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGER-TKIs is inevitable due to various mechanisms, such as the secondary mutation (T790M), activation of alternative pathways (c-Met. HGF, AXL), abernmce of the downstream pathways (K-RAS mutations, loss of PTEN), impahment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP) binding cassette (ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms tolEGFR-TKIs and provide potential targets for development of new therapeutic strategies. (c) 2015 Chinese Pharmaceutical Association and Institute of Modica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.