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Updated: Jun 1, 2025

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

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Development of PROTACs targeting estrogen receptor: an emerging technique for combating endocrine resistance

Rouming Peng1, Xin Liu1, Chun-Chi Chen1,2

  • 1State Key Laboratory of Biocatalysis and Enzyme Engineering, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, School of Life Sciences, Hubei University Wuhan 430062 China guoreyting@hubu.edu.cn jianmin@hubu.edu.cn.

RSC Medicinal Chemistry
|January 17, 2025
PubMed

Insights

Estrogen receptor proteolysis-targeting chimeras (ER PROTACs) offer a novel strategy to degrade estrogen receptors, potentially overcoming resistance to endocrine therapies for ER-positive breast cancer. This review covers their design, efficacy, and clinical trials, highlighting future opportunities and challenges.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Endocrine therapies are successful for ER-positive breast cancer but face resistance.
  • Estrogen receptor (ER) is a key target in breast cancer treatment.

Purpose of the Study:

  • To review the drug design, efficacy, and early clinical trials of ER PROTACs.
  • To highlight opportunities and challenges in developing ER PROTACs for clinical use.

Main Methods:

  • Review of existing literature on ER PROTACs.
  • Analysis of drug design principles for ER PROTACs.
  • Summary of preclinical and early clinical trial data.

Main Results:

  • ER PROTACs utilize the ubiquitin-proteasome system to degrade ER.
  • This degradation mechanism may bypass common resistance pathways.
  • Early data suggest potential efficacy and feasibility of ER PROTACs.

Conclusions:

  • ER PROTACs represent a promising therapeutic strategy for ER-positive breast cancer.
  • Further research and development are needed to overcome challenges for clinical translation.
  • This emerging technology presents significant academic and industrial opportunities.

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