2. Academic Validation
  3. Selective Estrogen Receptor Degraders (SERDs): A Promising Strategy for Estrogen Receptor Positive Endocrine-Resistant Breast Cancer

Selective Estrogen Receptor Degraders (SERDs): A Promising Strategy for Estrogen Receptor Positive Endocrine-Resistant Breast Cancer

  • J Med Chem. 2020 Dec 24;63(24):15094-15114. doi: 10.1021/acs.jmedchem.0c00913.
Yunlong Lu 1 2,  Wukun Liu 1 3 4
Affiliations

Affiliations

  • 1 School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
  • 3 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.
  • 4 State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210023, P. R. China.
PMID: 33138369 DOI: 10.1021/acs.jmedchem.0c00913
Abstract

Estrogen receptor (ER) plays important roles in gene transcription and the proliferation of ER positive breast cancers. Selective modulation of ER has been a therapeutic target for this specific type of breast Cancer for more than 30 years. Selective Estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) have been demonstrated to be effective therapeutic approaches for ER positive breast cancers. Unfortunately, 30-50% of ER positive tumors become resistant to SERM/AI treatment after 3-5 years. Fulvestrant, the only approved selective Estrogen receptor Degrader (SERD), is currently an important therapeutic approach for the treatment of endocrine-resistant breast cancers. The poor pharmacokinetic properties of fulvestrant have inspired the development of a new generation of oral SERDs to overcome drug resistance. In this review, we describe recent advances in ERα structure, functions, and mechanisms of endocrine resistance and summarize the development of oral SERDs in both academic and industrial areas.

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