Selective degradation of the estrogen receptor in the treatment of cancers

Zunyuan Wang; Zhen Ma; Zhengrong Shen

doi:10.1016/j.jsbmb.2021.105848

Selective degradation of the estrogen receptor in the treatment of cancers

J Steroid Biochem Mol Biol. 2021 May:209:105848. doi: 10.1016/j.jsbmb.2021.105848. Epub 2021 Feb 18.

Authors

Zunyuan Wang¹, Zhen Ma¹, Zhengrong Shen²

Affiliations

¹ Institute of Materia Medica, Hangzhou Medical College, 310013 Hangzhou, Zhejiang, China.
² Institute of Materia Medica, Hangzhou Medical College, 310013 Hangzhou, Zhejiang, China. Electronic address: shenzr@zjams.com.cn.

PMID: 33610801
DOI: 10.1016/j.jsbmb.2021.105848

Abstract

Estrogen receptor subtype α (ERα) plays key roles in breast cancers, and has been a target for endocrine therapy for a long time. Unfortunately, long-term treatment by Aromatase Inhibitors (AIs) or Selective Estrogen Receptor Modulators (SERMs) could cause drug resistance and also would increase the risk for uterine cancer. Therefore, novel anti-breast cancer drugs based on different mechanisms of action have received significant attention, especially through the strategies of selective degradation of ER. In this article, the latest research progress of selective targeting ER for degradation, including Selective ER Downregulators (SERDs), Proteolysis Targeting Chimaeras (PROTACs) and other techniques, was reviewed, and the applications and problems to be solved were prospected.

Keywords: Breast cancer; Degradation; Endocrine therapy; Estrogen receptor.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Breast Neoplasms / drug therapy*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Female
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Receptors, Estrogen / genetics
Receptors, Estrogen / metabolism*
Selective Estrogen Receptor Modulators / pharmacology*

Substances

Receptors, Estrogen
Selective Estrogen Receptor Modulators