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MCF-7 cells long-term treated with Fulv plus Abema acquired ESR1 Y537S mutation and exhibited defective RSR and DDR

GSE314294 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2026/01/05 Platform GPL24676
Summary
ESR1 mutations are the leading cause of endocrine therapy resistance and progression in ER-positive metastatic breast cancer. ESR1 mutations are detected in ~50% of metastatic breast cancer patients, and identification of effective targeted therapeutics are critically needed. Here, we identified enrichment of dysregulated replication stress and DNA damage responses in multiple ESR1 mutant models. Long-term treatment with endocrine therapy Fulvestrant plus the CDK4/6 inhibitor abemaciclib led to the emergence of a Y537S ESR1 mutation in a cell line, which exhibited dysregulation of replication stress response, enhanced DNA damage response, and synergistic responses to inhibitors of these pathways.
Published in
Defective DNA Damage Response Is a Targetable Therapeutic Vulnerability in ESR1-Mutant Breast Cancer
Herzog SK, Stevens JH, Gu G et al. · Cancer research 2026 · PMID 41499130 · doi:10.1158/0008-5472.CAN-24-3891
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Also filed as BioProject PRJNA1390673 and SRA study SRP656397. Searching any of these in the dataset finder brings you back here.

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