Cited by 122Estrogen and related hormone effectsAdvanced Breast Cancer TherapiesBreast Cancer Treatment Studies

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

Lu, Yunlong, Liu, Wukun·2020·Journal of Medicinal Chemistry

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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Crossref · 10.1021/acs.jmedchem.0c00913

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177 of 177 references verified0 citation errors · 0 not checkable

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Authors
Lu, Y., & Liu, W.
Affiliations
Nanjing University of Chinese Medicine (CN)
Corresponding author
  • Lu, Yunlong
  • Liu, Wukun
Venue
Journal of Medicinal Chemistry
Published
2020-11-02
Volume
63
Issue
24
Pages
15094-15114
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W3094721087
Cited by
119
References
178
Citations by year
2026: 20 · 2025: 22 · 2024: 29 · 2023: 29 · 2022: 12 · 2021: 7
FWCI
7.46
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Jiangsu Provincial Department of Education
  • State Key Laboratory of Natural Medicines (SKLNMKF201712, SKLNMKF201808)
  • Six Talent Peaks Project in Jiangsu Province (SWYY-069)
  • National Natural Science Foundation of China (81703337)
  • Priority Academic Program Development of Jiangsu Higher Education Institutions
  • State Key Laboratory of Coordination Chemistry, Nanjing University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Advanced Breast Cancer Therapies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords
selective estrogen receptor degrader, estrogen receptor-positive breast cancer, endocrine therapy resistance, fulvestrant, aromatase inhibitors, selective estrogen receptor modulators, drug resistance mechanisms
MeSH terms
Fulvestrant, Breast Neoplasms, Clinical Trials as Topic, Female, Humans, Steroids, Structure-Activity Relationship, Signal Transduction, Drug Resistance, Neoplasm, Selective Estrogen Receptor Modulators, Aromatase Inhibitors, Estrogen Receptor alpha

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