fulvestrant + entinostat

Fulvestrant + entinostat is an investigational combination therapy for hormone receptor–positive, HER2-negative advanced breast cancer. Fulvestrant is a selective estrogen receptor downregulator (SERD) that binds to, inhibits, and degrades estrogen receptor (ER), disrupting estrogen signaling and leading to tumor growth inhibition and apoptosis in ER-positive tumors. Entinostat is a class I selective oral histone deacetylase inhibitor (HDACi) that alters gene expression by modifying chromatin structure, aiming to re-sensitize breast cancer cells to endocrine (anti-estrogen) treatments by reversing mechanisms of acquired resistance. This combination is under clinical investigation (primarily phase 1 and 2 studies) in patients who develop resistance to prior endocrine therapies.