The mechanism and response strategies of osimertinib resistance in non-small cell lung cancer
LI Pan
TAN Kunming
LV Xinwu
YI Yanmei
Abstract：With the in-depth research on the pathogenesis of lung cancer,driver gene-guided molecular targeted therapy has made breakthrough progress in the treatment of non-small cell lung cancer.Tyrosine kinase inhibitors targeting the epidermal growth factor receptor(EGFR)have been recommended as first-line agents for EGFR mutation-positive non-small cell lung cancer.As a third-generation tyrosine kinase inhibitor,osimertinib shows much better clinical response and efficacy than first-and second-generation tyrosine kinase inhibitors.Despite the remarkable success of osimertinib in both first-and second-line NSCLC treatment,the inevitable acquired resistance has become an urgent clinical issue.This article reviews the primary resistance mechanisms of osimertinib BIM(Bcl-2 interacting mediator of cell death)and PTEN(phosphatase and tensin homologue)deficiency and secondary resistance mechanisms(EGFR-dependent and non-dependent resistance mechanisms)of osimertinib in non-small cell lung cancer,and the coping strategies formulated for it,including osimertinib combined with other drug treatments,allosteric EGFR inhibitors and multi-target inhibitors are used to provide a reference for enhancing the effect of targeted therapy for clinical non-small cell lung cancer.
Keywords：non-small cell lung cancerosimertinib resistancetumor drug resistancetargeted therapyepidermal growth factor receptor
Publication Date：2025-06-30
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：9( 293-301 )