Drug Resistance Mechanism of Third Generation EGFR-TKI and Therapeutic Strategy of Drug Combination
Epidermal growth factor receptor(EGFR)is a receptor tyrosine kinase that participates in physiological processes such as cell proliferation,division,and differentiation.EGFR plays an important role in the occurrence and development of tumors.In targeted treatment of non-small cell lung cancer,tyrosine kinase inhibitors(TKIs)targeting EGFR have achieved significant efficacy.However,with the emergence of mutations such as EGFR T790M,patients may develop resistance to the first and second-generation EGFR TKI therapy.Therefore,the third generation EGFR TKI,represented by Osimertinib,has achieved good results in patients with EGFR T790M mutations.However,some patients still develop acquired drug resistance after third generation EGFR TKI treatment.Currently,the drug resistance mech-anisms are mainly divided into two types:EGFR dependent(mutations in the EGFR kinase domain)and EGFR independent(activation of abnormal bypass signals and downstream signal pathways,and histolog-ical phenotypic changes).This article comprehensively reviews and summarizes the structure and main drug resistance mechanisms of the third generation TKI,and the treatment strategies after drug resistance and the possible directions for overcoming EGFR TKI resistance in the future are also analyzed.
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