Development of Osimertinib Resistant Mouse Models for Preclinical Evaluation

As a first-line treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutations, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved patient prognosis by means of their targeted treatment mechanisms. Osimertinib, a third-generation EGFR-TKI, exhibits dual therapeutic advantages through its robust inhibitory activity against both common EGFR-sensitive mutations and challenging rare EGFR variants. Notably, this targeted agent has shown significant effectiveness in overcoming acquired resistance mechanisms developed during first- and second-generation EGFR-TKI therapies. However, its therapeutic efficacy is compromised by acquired EGFR-C797S mutations (including EGFR triple mutations Del19/T790M/C797S or L858R/T790M/C797S), bypass activation pathways (e.g., MET amplification, HER2 amplification), histological/phenotypic transformation, and other latent mechanisms.