Resistant Mouse Models for Advancing Third-Generation EGFR-TKI Drug Development

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), has transformed the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). However, acquired resistance mediated by EGFR C797 mutations remains a major unmet clinical need. GemPharmatech has developed a panel of Osimertinib-resistant preclinical models using both gene-editing and chronic drug-exposure strategies. This includes the NCI-H1975-C797S triple-mutant cell line (EGFR L858R/T790M/C797S), along with additional resistant lines generated through prolonged osimertinib exposure. These models were thoroughly validated in vitro and in vivo, exhibiting stable and robust resistance phenotypes. Together, they provide powerful translation platforms for elucidating resistance mechanisms and evaluating next-generation EGFR-targeted therapies.