ArticleCancer science2025
Novel Approach to Overcome Osimertinib Resistance Using Bromodomain and Extra-Terminal Domain Inhibitors.
Article in Cancer science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
2 citing papers in PubMed.
- Advances in understanding the mechanisms underlying acquired resistance to third-generation tyrosine kinase inhibitors in non-small cell lung cancer.Frontiers in cell and developmental biology · 2026Review
- Bromodomain and extra-terminal proteins in solid tumors: regulators of immune microenvironment and emerging therapeutic targets.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
21 authors.
Funding
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 modifications. FGF1 induced osimertinib resistance, and its suppression attenuated resistance. Bromodomain and extra-terminal domain inhibitors combined with osimertinib overcame osimertinib resistance by reducing FGF1 expression. Increased FGF1 expression was observed in osimertinib-resistant clinical samples. This combination therapy was effective in cell lines and mouse xenograft models. These results suggest targeting histone modifications using bromodomain and extra-terminal domain inhibitors as a novel approach to overcoming osimertinib resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.