Novel syngeneic models for evaluating therapies targeting EGFRL858R/T790Mand EGFRL858R/T790M/C979Sresistance mutations in NSCLC
Presenter: Leon Xu Session: Experimental Chemoprevention and Interception: Data and Tools Time: 4/19/2026 2:00:00 PM → 4/19/2026 5:00:00 PM
Authors
Lei Ci , Kai Zhou , Jiangyan Liu , Ruilin Sun GenoBioTX LLC, Suger Land, TX
Abstract
Both the first and second-generation EGFR-TKIs drugs have markedly improved the survival of NSCLC patients with activating EGFR mutations. However a secondary T790M mutation rapidly drives resistance towards these drugs. Third-generation EGFR-TKIs potently suppress the T790M mutant, but the subsequent C797S mutation abolishes their covalent binding, leaving no currently approved targeted options. Therefore, our laboratory generated conditional knock-in C57BL/6 mice harboring human EGFR L858R/T790M or EGFR L858R/T790M/C979S , which quickly develop spontaneous NSCLC and yield primary tumor cell lines.In syngeneic, immune-competent C57BL/6 hosts, the fourth-generation TKI under research, BLU-945, markedly inhibited both EGFR L858R/T790M and EGFR L858R/T790M/C979S tumor growth. In contrast, osimertinib was effective only against EGFR L858R/T790M , but failing against the EGFR L858R/T790M/C979S mutation. This demonstrates how our novel mouse models faithfully recapitulate and allow the reversal of osimertinib resistance in vivo .
Disclosure
L. Ci, Shanghai Model Organisms Center, Inc. Other, Parent Company. K. Zhou, Shanghai Model Organisms Center, Inc. Other, Parent Company. J. Liu, Shanghai Model Organisms Center, Inc. Other, Parent Company. R. Sun, Shanghai Model Organisms Center, Inc. Other, Parent Company.
Cited in
Control: 5717 · Presentation Id: 6767 · Meeting 21436