Targeting the Estrogen Receptor (ER) for the Treatment of Breast Cancer: Recent Advances and Challenges

Abstract

Estrogen receptor alpha (ERα) is a well-established therapeutic target for the treatment of ER-positive (ER+) breast cancers. Despite the tremendous successes achieved by tamoxifen, a selective estrogen receptor modulator, and aromatase inhibitors (AIs), resistance to these therapies is a major clinical problem. Therefore, induced protein degradation and covalent inhibition have been pursued as new therapeutic approaches to target ERα. This review summarizes recent progress in the discovery and development of oral selective ER degraders (SERDs), CERANs (complete estrogen receptor antagonists), SERCAs (selective estrogen receptor covalent antagonists), and PROTAC (proteolysis targeting chimera) ER degraders. We focus on those compounds which have been advanced into clinical development