ArticleMolecular cancer therapeutics2015
Multiple molecular subtypes of triple-negative breast cancer critically rely on androgen receptor and respond to enzalutamide in vivo.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line.Molecules (Basel, Switzerland) · 2022Pooled it
- A Phase II Clinical Trial of Pembrolizumab and Enobosarm in Patients with Androgen Receptor-Positive Metastatic Triple-Negative Breast Cancer.The oncologist · 2021Trial
- TBCRC 032 IB/II Multicenter Study: Molecular Insights to AR Antagonist and PI3K Inhibitor Efficacy in Patients with ARClinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Phase II Study of Dehydroepiandrosterone in Androgen Receptor-Positive Metastatic Breast Cancer.The oncologist · 2019Trial
- Matrix Stiffness Directs Stemness Signatures in Breast Cancer.Advanced healthcare materials · 2026Article
- Targeting microRNA let-7b-5p-mediated aberrant androgen receptor signaling for prevention of hormone receptor-negative breast cancer.NPJ breast cancer · 2026Article
- Androgens are a Key Factor Affecting Immune Related Diseases.The world journal of men's health · 2026Review
- Targeted Therapies for Each Subtype of Breast Cancer.MedComm · 2026Review
- Exploring Cutting-Edge Strategies for the Management of Triple-Negative Breast Cancer Through Drug Repurposing.Current topics in medicinal chemistry · 2026Review
- Androgen receptor interacts with c-Myc to regulate macrophage-osteoclast axis and drive bone metastasis in triple negative breast cancer.British journal of cancer · 2025Article
- Biomarkers, isolation methods, and therapeutic implications of breast cancer stem cells.Cancer pathogenesis and therapy · 2025Review
- Tailored therapies for triple-negative breast cancer: current landscape and future perceptions.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting CDK7 Enhances the Antitumor Efficacy of Enzalutamide in Androgen Receptor-Positive Triple-Negative Breast Cancer by Inhibiting c-MYC-mediated Tumorigenesis.Molecular cancer therapeutics · 2025Article
- Uncovering a Novel Role of ROR1 in the Epigenetic Regulation of Tumor Suppressor Gene CREB3L1 in Triple-Negative Breast Cancer Cells.Biomolecules · 2025Article
- Looking beyond the ER, PR, and HER2: what's new in the ARsenal for combating breast cancer?Reproductive biology and endocrinology : RB&E · 2025Review
- Unveiling the Potential of S4 on Non-small Cell Lung Cancer Cells: Impact on Proliferation, Apoptosis, Senescence, and Metabolome Profile.Anti-cancer agents in medicinal chemistry · 2025Article
- The Landscape of Potential Targeted Treatments and Chemotherapy Efficacy Biomarkers for TNBC.Breast cancer (Dove Medical Press) · 2025Review
- Clinical and immune responses to neoadjuvant fulvestrant with or without enzalutamide in ER+/Her2- breast cancer.NPJ breast cancer · 2024Article
- Integrated Metabolomics and Transcriptomics Analysis of Anacardic Acid Inhibition of Breast Cancer Cell Viability.International journal of molecular sciences · 2024Article
- Incidence and Prognostic Significance of Androgen Receptors (AR) in Indian Triple-Negative Breast Cancer (TNBC).Indian journal of surgical oncology · 2024Article
74 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) has the lowest 5-year survival rate of invasive breast carcinomas, and currently there are no approved targeted therapies for this aggressive form of the disease. The androgen receptor (AR) is expressed in up to one third of TNBC and we find that all AR(+) TNBC primary tumors tested display nuclear localization of AR, indicative of transcriptionally active receptors. While AR is most abundant in the "luminal AR (LAR)" molecular subtype of TNBC, here, for the first time, we use both the new-generation anti-androgen enzalutamide and AR knockdown to demonstrate that the other non-LAR molecular subtypes of TNBC are critically dependent on AR protein. Indeed, AR inhibition significantly reduces baseline proliferation, anchorage-independent growth, migration, and invasion and increases apoptosis in four TNBC lines (SUM159PT, HCC1806, BT549, and MDA-MB-231), representing three non-LAR TNBC molecular subtypes (mesenchymal-like, mesenchymal stem-like, and basal-like 2). In vivo, enzalutamide significantly decreases viability of SUM159PT and HCC1806 xenografts. Furthermore, mechanistic analysis reveals that AR activation upregulates secretion of the EGFR ligand amphiregulin (AREG), an effect abrogated by enzalutamide in vitro and in vivo. Exogenous AREG partially rescues the effects of AR knockdown on proliferation, migration, and invasion, demonstrating that upregulation of AREG is one mechanism by which AR influences tumorigenicity. Together, our findings indicate that non-LAR subtypes of TNBC are AR dependent and, moreover, that enzalutamide is a promising targeted therapy for multiple molecular subtypes of AR(+) TNBC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.