Novel Approach to Overcome Osimertinib Resistance Using Bromodomain and Extra-Terminal Domain Inhibitors.

ABSTRACT: Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, is the first-line therapy for lung cancer harboring EGFR mutations. The mechanisms underlying osimertinib resistance are diverse, with approximately half remaining unknown. Epigenetic dysregulation is implicated in drug resistance; however, the mechanisms remain unclear. Therefore, we investigated epigenetic involvement in osimertinib resistance and its therapeutic potential. We established osimertinib-resistant cells and used an assay for transposase-accessible chromatin using sequencing to evaluate chromatin accessibility, finding significant changes post-resistance. Combining the assay for transposase-accessible chromatin and RNA sequencing data, we identified FGF1 as a resistance-related gene regulated by histone modificat

SUBMITTER: Miyashita Y 

PROVIDER: S-EPMC12044652 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature