New generation estrogen receptor-targeted agents in breast cancer: present situation and future prospectives

Abstract

Endocrine therapy that blocks estrogen receptor signaling has been effective for decades as a primary treatment choice for breast cancer patients expressing the estrogen receptor. However, the issue of drug resistance poses a significant clinical challenge. It is therefore critically important to create new therapeutic agents that can suppress ERα activity, particularly in cases of ESR1 mutations. This review highlights recent efforts in drug development of next generation ER-targeted agents, including oral selective ER degraders, proteolysis-targeting chimera ER degraders, and other innovative molecules, such as complete estrogen receptor antagonists and selective estrogen receptor covalent antagonists. The drug design, efficacy, and clinical trials for each compound are detailed herein.