| Non-small cell lung cancer (NSCLC) is the most common histological subtype of lung cancer, and epidermal growth factor receptor (EGFR) mutations represent an important oncogenic driver. The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has significantly improved survival outcomes in patients with advanced EGFR-mutant NSCLC; however, most patients inevitably develop acquired resistance during continued treatment, limiting the long-term efficacy of targeted therapy. The mechanisms of acquired resistance to EGFR-TKIs are highly heterogeneous and mainly include secondary EGFR mutations, activation of bypass signaling pathways, acquisition of gene fusions, abnormalities in downstream signaling pathways, and phenotypic or histological transformation; in some patients, the specific resistance mechanism remains unidentified with currently available testing methods. This review summarizes the major molecular mechanisms of acquired resistance to EGFR-TKIs and the corresponding advances in clinical research. |
