中文摘要：

Since the discovery that non-small cell lung cancer(NSCLC) is driven by epidermal growth factor receptor(EGFR) mutations, the EGFR tyrosine kinase inhibitors(EGFR-TKIs, e.g., ge fi tinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation(T790M), activation of alternative pathways(c-Met, HGF, AXL), aberrance of the downstream pathways(K-RAS mutations, loss of PTEN), impairment 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 to EGFR-TKIs and provide potential targets for development of new therapeutic strategies.

英文摘要：

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.