Next-Generation Estrogen Receptor–Targeted Therapeutics

Abstract

Estrogen receptor (ER) α is expressed in the vast majority of breast cancers and is one of the most successfully prosecuted drug targets in oncology, with multiple classes of endocrine therapies approved for the treatment of ER+ breast cancer. These existing agents are highly active, both as single agents and as combination partners for other targeted therapies, and have significantly benefited patients. However, each of these standard-of-care (SOC) therapies has liabilities that allow for the reengagement of ER signaling as a mechanism of resistance. Data supporting the continued dependence of tumors on ER signaling following exposure to SOC agents have underpinned an extraordinary reenergizing of academic, biotechnology, and pharmaceutical groups pursuing next-generation ER-targeted therapies. The hypothesis that there remains an opportunity to bring further meaningful benefit to patients through fully optimized ER-targeted therapies is currently being investigated in the clinic.