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

Jian Min1, Xin Liu1, Rouming Peng1

  • 1National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, School of Life Sciences, Hubei University, Wuhan, 430062, China.

Acta Materia Medica
|October 7, 2024
PubMed

Insights

New therapies are crucial for breast cancer patients with estrogen receptor (ER) positive tumors who develop resistance to endocrine therapy. This review covers next-generation ER-targeted agents like oral selective ER degraders (SERDs) and PROTACs.

Area of Science:

  • Oncology
  • Endocrinology
  • Pharmacology

Background:

  • Endocrine therapy targeting the estrogen receptor (ER) is a cornerstone treatment for ER-positive breast cancer.
  • Drug resistance, particularly with ESR1 mutations, limits the long-term efficacy of current ER-targeted therapies.
  • Development of novel agents to overcome resistance and suppress ERα activity is a critical clinical need.

Purpose of the Study:

  • To review recent advancements in the development of next-generation ER-targeted agents for breast cancer.
  • To highlight novel therapeutic strategies aimed at overcoming endocrine resistance.
  • To provide an overview of drug design, efficacy, and clinical trial data for emerging ER-targeted compounds.

Main Methods:

  • Literature review of recent research and clinical trials on novel ER-targeted agents.
  • Analysis of drug design principles for next-generation therapies.
  • Summary of efficacy and clinical data for compounds targeting ERα, including those effective against ESR1 mutations.

Main Results:

  • Several classes of next-generation ER-targeted agents are under development, including oral selective ER degraders (SERDs) and proteolysis targeting chimera (PROTAC) ER degraders.
  • Innovative molecules such as complete estrogen receptor antagonists (CERANs) and selective estrogen receptor covalent antagonists (SERCAs) show promise.
  • These agents are designed to more effectively suppress ERα activity and overcome resistance mechanisms, including ESR1 mutations.

Conclusions:

  • Next-generation ER-targeted agents represent a promising frontier in overcoming endocrine resistance in breast cancer.
  • Oral SERDs, PROTACs, CERANs, and SERCAs offer diverse mechanisms to inhibit ER signaling and degrade the receptor.
  • Further clinical evaluation is essential to establish the role of these novel agents in patient treatment.
Keywords:
Estrogen receptorPROTACSERDendocrine resistant breast cancer

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