Defective DNA Damage Response Is a Targetable Therapeutic Vulnerability in ESR1-Mutant Breast Cancer.

UNLABELLED: ESR1 mutations are the leading cause of endocrine therapy resistance and progression in estrogen receptor (ER)-positive metastatic breast cancer. ESR1 mutations are detected in ∼50% of patients with metastatic breast cancer, and identification of effective targeted therapeutics is critically needed. In this study, we identified enrichment of dysregulated replication stress and DNA damage responses in multiple ESR1-mutant models. Targeting the replication stress response utilizing che...