Estrogen Blockers Raw Materials

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

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

Perspective June 28, 2023

Authors

Rohan Kalyan Rej Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States
Junius Eugene Thomas II Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States Program in Chemical Biology, University of Michigan, Ann Arbor, Michigan 48109, United States
Ranjan Kumar Acharyya Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States
James Michael Rae Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, United States
Shaomeng Wang Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, United States Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, United States Program in Chemical Biology, University of Michigan, Ann Arbor, Michigan 48109, United States Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States (734) 615-0362

Journal Information

Journal of Medicinal Chemistry

Cite this: J. Med. Chem. 2023, 66, 13

Published June 28, 2023

review-article

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 with tamoxifen, a selective ER 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 Perspective summarizes recent progress in the discovery and development of oral selective ER degraders (SERDs), complete estrogen receptor antagonists (CERANs), selective estrogen receptor covalent antagonists (SERCAs), and proteolysis targeting chimera (PROTAC) ER degraders. We focus on those compounds which have been advanced into clinical development.

ACS Publications

Cited By

This article is cited by 75 publications.

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