entinostat + aromatase inhibitor

**Entinostat + aromatase inhibitor** is a combination therapy regimen used primarily in oncology clinical trials for the treatment of advanced hormone receptor-positive, HER2-negative breast cancer. **Entinostat** is an orally bioavailable, benzamide-derived small molecule that acts as a selective inhibitor of class I histone deacetylases (HDACs). **Aromatase inhibitors** (such as exemestane, letrozole, or anastrozole) are a class of drugs that block the aromatase enzyme and thus inhibit estrogen biosynthesis. The rationale for combining these agents is that entinostat may resensitize tumors to hormonal therapy—overcoming acquired resistance to aromatase inhibitors by modulating estrogen receptor (ER) expression and downstream pathways. Clinical studies, notably with entinostat + exemestane, demonstrated improvement in progression-free and overall survival in phase II, but not in phase III trials.