Overcoming EGFRG724S-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors

Abstract excerpt

Abstract The emergence of acquired resistance against targeted drugs remains a major clinical challenge in lung adenocarcinoma patients. In a subgroup of these patients we identified an association between selection of EGFR T790M -negative but EGFR G724S -positive subclones and osimertinib resistance. We demonstrate that EGFR G724S limits the activity of third-generation EGFR inhibitors both in vitro and in vivo....

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