2024 Targeted Therapies for Lung Cancer (TTLC) - Abstracts & Posters-PP01.34 Viray

PP01.34 Viray - Poster

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The document presents a study on the characterization of on-target resistance to EGFR exon 20 insertion mutation active inhibitors in lung cancer cells. The research evaluates the response of various EGFR mutants to different EGFR-TKIs, such as osimertinib, poziotinib, mobocertinib, zipalertib, furmonertinib, and sunvozertinib. The study examines how the presence of EGFR-T790M or EGFR-C797S mutations affects the sensitivity or resistance to these inhibitors. Results indicate that the most common EGFR exon 20 insertion mutations show susceptibility to resistance to mobocertinib mediated by EGFR-T790M or EGFR-C797S. The study also highlights that furmonertinib and sunvozertinib exhibit favorable therapeutic windows in cells with EGFR mutations, while EGFR-C797S mutation leads to resistance to multiple inhibitors. This research aims to provide insights into overcoming resistance mechanisms and guide the development of more effective EGFR mutation inhibitors. The methods involved preclinical models, cell proliferation assays, and immunoblotting to assess the impact of mutations on drug sensitivity. Overall, the study emphasizes the importance of understanding resistance mechanisms to effectively treat EGFR exon 20 insertion mutations in lung cancer, paving the way for the development of novel inhibitors with improved therapeutic efficacy.

Keywords

EGFR exon 20 insertion mutation

on-target resistance

lung cancer cells

EGFR-TKIs

osimertinib

poziotinib

mobocertinib

zipalertib

furmonertinib

sunvozertinib