Abstract
The estrogen receptor α (ERα) has proven to be the single most important target in breast cancer over the last 30 years. The use of the selective ER modulator (SERM) tamoxifen for the treatment and prevention of breast cancer has changed therapeutics. The SERM raloxifene, approved for the treatment of osteoporosis, lacks tamoxifens increased risk for endometrial cancer and is being evaluated for the prevention of breast cancer. Other SERMs approved or under development for use against breast cancer or osteoporosis include toremifene, GW5638, GW7604 (the active metabolite of GW5638), idoxifene, lasofoxifene, arzoxifene, bazedoxifene, EM-800 and acolbifene (the active metabolite of EM- 800). Aromatase inhibitors (AIs) have recently proven to be more efficacious than tamoxifen as first-line therapy, efficacious for second-line therapy (e.g. against tamoxifen-resistant disease), and useful for extended adjuvant therapy after tamoxifen. The AIs include the non-steroidal agents letrozole and anastrole, and the steroidal agent exemestane. The pure antiestrogen fulvestrant has proven to be just as effective as AIs. Other pure antiestrogens, ZK-703, ZK-253, RU 58668 and TAS-108 show great promise. The development of resistance to endocrine therapy remains a clinically important problem, and laboratory models based on human breast cancer cells grown as tumors in immune-compromised mice have led to important insights into this problem. Progesterone receptor-negative status of ER-positive breast cancers may reflect altered growth factor receptor signaling, and helps to explain why this subclass of tumors exhibits lower response rates to tamoxifen compared to cancers typed progesterone receptor-positive. Crosstalk among plasma membrane-localized ER, growth factor receptor signaling, and nuclear-localized ER provide further insights into antihormonal-resistant breast cancer.
Keywords: Estrogen receptor, selective estrogen receptor modulator, aromatase inhibitor, pure antiestrogen, breast cancer, antihormonal resistance
Current Topics in Medicinal Chemistry
Title: Estrogen Receptors as Therapeutic Targets in Breast Cancer
Volume: 6 Issue: 3
Author(s): Eric A. Ariazi, Jennifer L. Ariazi, Fernando Cordera and V. Craig Jordan
Affiliation:
Keywords: Estrogen receptor, selective estrogen receptor modulator, aromatase inhibitor, pure antiestrogen, breast cancer, antihormonal resistance
Abstract: The estrogen receptor α (ERα) has proven to be the single most important target in breast cancer over the last 30 years. The use of the selective ER modulator (SERM) tamoxifen for the treatment and prevention of breast cancer has changed therapeutics. The SERM raloxifene, approved for the treatment of osteoporosis, lacks tamoxifens increased risk for endometrial cancer and is being evaluated for the prevention of breast cancer. Other SERMs approved or under development for use against breast cancer or osteoporosis include toremifene, GW5638, GW7604 (the active metabolite of GW5638), idoxifene, lasofoxifene, arzoxifene, bazedoxifene, EM-800 and acolbifene (the active metabolite of EM- 800). Aromatase inhibitors (AIs) have recently proven to be more efficacious than tamoxifen as first-line therapy, efficacious for second-line therapy (e.g. against tamoxifen-resistant disease), and useful for extended adjuvant therapy after tamoxifen. The AIs include the non-steroidal agents letrozole and anastrole, and the steroidal agent exemestane. The pure antiestrogen fulvestrant has proven to be just as effective as AIs. Other pure antiestrogens, ZK-703, ZK-253, RU 58668 and TAS-108 show great promise. The development of resistance to endocrine therapy remains a clinically important problem, and laboratory models based on human breast cancer cells grown as tumors in immune-compromised mice have led to important insights into this problem. Progesterone receptor-negative status of ER-positive breast cancers may reflect altered growth factor receptor signaling, and helps to explain why this subclass of tumors exhibits lower response rates to tamoxifen compared to cancers typed progesterone receptor-positive. Crosstalk among plasma membrane-localized ER, growth factor receptor signaling, and nuclear-localized ER provide further insights into antihormonal-resistant breast cancer.
Export Options
About this article
Cite this article as:
Ariazi A. Eric, Ariazi L. Jennifer, Cordera Fernando and Jordan Craig V., Estrogen Receptors as Therapeutic Targets in Breast Cancer, Current Topics in Medicinal Chemistry 2006; 6 (3) . https://dx.doi.org/10.2174/156802606776173483
DOI https://dx.doi.org/10.2174/156802606776173483 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Heterocyclic Scaffolds: Centrality in Anticancer Drug Development
Current Drug Targets Lipid Metabolism and Mitochondria: Cross Talk in Cancer
Current Drug Targets A Novel Marine Drug, SZ–685C, Induces Apoptosis of MMQ Pituitary Tumor Cells by Downregulating miR–200c
Current Medicinal Chemistry Cancer Stem Cells: How can we Target them?
Current Medicinal Chemistry Antiproliferative and Proapoptotic Effects of Proteasome Inhibitors and their Combination with Histone Deacetylase Inhibitors on Leukemia Cells
Cardiovascular & Hematological Disorders-Drug Targets Potential Role of Bioactive Lipids in Rheumatoid Arthritis
Current Pharmaceutical Design Personalizing HER2-Targeted Therapy in Metastatic Breast Cancer Beyond HER2 Status: What We Have Learned from Clinical Specimens
Current Pharmacogenomics and Personalized Medicine Garlic (<i>Allium sativum</i> L.): Its Chemistry, Nutritional Composition, Toxicity, and Anticancer Properties
Current Topics in Medicinal Chemistry The mTOR Signaling Network: Insights from Its Role During Embryonic Development
Current Medicinal Chemistry Ellipticines as DNA-Targeted Chemotherapeutics
Current Medicinal Chemistry Quinone Methide Bioactivation Pathway: Contribution to Toxicity and/or Cytoprotection?
Current Organic Chemistry Lynch Syndrome Identification in Endometrial Cancer Patients: Should Universal Screening be Used for all Histologies?
Current Women`s Health Reviews MicroRNAs: Potential Diagnostic and Therapeutic Targets for Breast Cancer
Epigenetic Diagnosis & Therapy (Discontinued) Recent Advances in Research on the Most Novel Carbonic Anhydrases,CA XIII and XV
Current Pharmaceutical Design Genetic Susceptibility to Endometrial Cancer
Current Women`s Health Reviews Synthetic Lethality-Based Therapeutics: Perspectives for Applications in Colorectal Cancer
Current Cancer Drug Targets PI3K/Akt/JNK/c-Jun Signaling Pathway is a Mediator for Arsenite- Induced Cyclin D1 Expression and Cell Growth in Human Bronchial Epithelial Cells
Current Cancer Drug Targets Editorial [Hot topic: Transportalopathy and Vascular Cell Dysfunction (Guest Editor: Luis Sobrevia)]
Current Vascular Pharmacology The Role of Hypoxia in Endometrial Cancer
Current Pharmaceutical Biotechnology Targeted Taxane Delivery Systems: Recent Advances
Drug Delivery Letters