Abstract
Estrogen receptor-alpha positive (ER+) breast cancer constitutes 70-75% of the disease incidence. Tamoxifen has been the basis of endocrine therapy for patients with ER+ breast cancer for more than three decades. The treatment reduces the annual mortality rate of breast cancer by 31%, and remains the most effective targeted cancer therapy. However, approximately one-third of patients treated with adjuvant tamoxifen suffer from aggressive recurrent disease. Resistance to tamoxifen, thus, remains a major challenge in providing effective treatments for these patients. In an effort to overcome the resistance, intensive research has been conducted to understand the underlying mechanisms; this has resulted in the identification of complex factors/pathways contributing to tamoxifen resistance, including modulations of the ERsignaling, upregulation of a set of growth factor receptor networks (HER2, EGFR, FGFR, and IGF1R), alterations of the PI3K-PTEN/AKT/mTOR pathway, and an elevation of the NF-κB signaling. Despite these advances, our understanding of the acquired resistance remains fragmented and there is a lack of a platform to integrate these diversified molecular factors/ pathways into a cohesive mechanistic model. Nonetheless, at the cellular level, it is becoming increasingly recongnized that cancer stem cells (CSCs) are key in driving cancer metastasis and therapy resistance. Likewise, evidence is emerging for the critical contributions of breast cancer stem cells (BCSCs) to tamoxifen resistance. In this review, we will discuss these recent developments of BCSC-mediated resistance to tamoxifen and the contributions of those demonstrated molecular factors/pathways to BCSC expansion during the emergency of tamoxifen resistance.
Keywords: Breast cancer, breast cancer stem cells, endocrine therapy, estrogen receptor, tamoxifen, tamoxifen resistance.
Current Medicinal Chemistry
Title:Factors Promoting Tamoxifen Resistance in Breast Cancer via Stimulating Breast Cancer Stem Cell Expansion
Volume: 22 Issue: 19
Author(s): Diane Ojo, Fengxiang Wei, Yun Liu, Enli Wang, Hongde Zhang, Xiaozeng Lin, Nicholas Wong, Anita Bane and Damu Tang
Affiliation:
Keywords: Breast cancer, breast cancer stem cells, endocrine therapy, estrogen receptor, tamoxifen, tamoxifen resistance.
Abstract: Estrogen receptor-alpha positive (ER+) breast cancer constitutes 70-75% of the disease incidence. Tamoxifen has been the basis of endocrine therapy for patients with ER+ breast cancer for more than three decades. The treatment reduces the annual mortality rate of breast cancer by 31%, and remains the most effective targeted cancer therapy. However, approximately one-third of patients treated with adjuvant tamoxifen suffer from aggressive recurrent disease. Resistance to tamoxifen, thus, remains a major challenge in providing effective treatments for these patients. In an effort to overcome the resistance, intensive research has been conducted to understand the underlying mechanisms; this has resulted in the identification of complex factors/pathways contributing to tamoxifen resistance, including modulations of the ERsignaling, upregulation of a set of growth factor receptor networks (HER2, EGFR, FGFR, and IGF1R), alterations of the PI3K-PTEN/AKT/mTOR pathway, and an elevation of the NF-κB signaling. Despite these advances, our understanding of the acquired resistance remains fragmented and there is a lack of a platform to integrate these diversified molecular factors/ pathways into a cohesive mechanistic model. Nonetheless, at the cellular level, it is becoming increasingly recongnized that cancer stem cells (CSCs) are key in driving cancer metastasis and therapy resistance. Likewise, evidence is emerging for the critical contributions of breast cancer stem cells (BCSCs) to tamoxifen resistance. In this review, we will discuss these recent developments of BCSC-mediated resistance to tamoxifen and the contributions of those demonstrated molecular factors/pathways to BCSC expansion during the emergency of tamoxifen resistance.
Export Options
About this article
Cite this article as:
Ojo Diane, Wei Fengxiang, Liu Yun, Wang Enli, Zhang Hongde, Lin Xiaozeng, Wong Nicholas, Bane Anita and Tang Damu, Factors Promoting Tamoxifen Resistance in Breast Cancer via Stimulating Breast Cancer Stem Cell Expansion, Current Medicinal Chemistry 2015; 22 (19) . https://dx.doi.org/10.2174/0929867322666150416095744
DOI https://dx.doi.org/10.2174/0929867322666150416095744 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Electrochemical Study of DNA Damaged by Oxidation Stress
Combinatorial Chemistry & High Throughput Screening Fast and Sensitive Liquid Chromatography Method for Simultaneous Determination of Methylisothiazolinone, Salicylic Acid and Parabens in Cosmetic Products
Current Analytical Chemistry Uptake of [¹⁸F]tetrafluoroborate in MCF-7 Breast Cancer Cells is Induced after Stimulation of the Sodium Iodide Symporter
Current Cancer Drug Targets Inventions Designed to Enhance Drug Delivery Across Epithelial and Endothelial Cells Through the Paracellular Pathway
Recent Patents on Drug Delivery & Formulation The Emerging Role of Poly(ADP-Ribose) Polymerase Inhibitors in Cancer Treatment
Current Drug Targets Oxidative/Nitrosative Stress and Immuno-inflammatory Pathways in Depression: Treatment Implications
Current Pharmaceutical Design Steroid Biosynthesis Inhibitors in the Therapy of Hypercortisolism: Theory and Practice
Current Medicinal Chemistry Synthesis and Antitumor Invasive Activity of Novel Ionone Alkaloid Derivatives
Letters in Drug Design & Discovery Editorial [Hot topic: Developing New Anti-Cancer Drugs (Guest Editor: Ricardo De Souza Pereira)]
Recent Patents on Anti-Cancer Drug Discovery Tubulin-Targeting Agents in Hybrid Drugs
Current Medicinal Chemistry The Role of Anaphylatoxins C3a and C5a in Regulating Innate and Adaptive Immune Responses
Inflammation & Allergy - Drug Targets (Discontinued) Cancer Microbiome; Opportunities and Challenges
Endocrine, Metabolic & Immune Disorders - Drug Targets Present Drug Therapy of Demyelinating Disorders
Current Drug Therapy Graphical Abstracts
Current Drug Delivery Chemopreventive Properties of Tolfenamic Acid: A Mechanistic Review
Current Medicinal Chemistry Mechanisms by which Stress Affects the Experimental and Clinical Inflammatory Bowel Disease (IBD): Role of Brain-Gut Axis
Current Neuropharmacology Astrocyte Signaling and Multiple Sclerosis
Current Signal Transduction Therapy Difference Gel Electrophoresis: Application in Quantitative Proteomics Research
Current Proteomics Targeting Key Transporters in Tumor Glycolysis as a Novel Anticancer Strategy
Current Topics in Medicinal Chemistry Design and Discovery of Novel Quinoxaline Derivatives as Dual DNA Intercalators and Topoisomerase II Inhibitors
Anti-Cancer Agents in Medicinal Chemistry