ArticleCancer research2016
Combined Treatment with Epigenetic, Differentiating, and Chemotherapeutic Agents Cooperatively Targets Tumor-Initiating Cells in Triple-Negative Breast Cancer.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line.Molecules (Basel, Switzerland) · 2022Pooled it
- Differentiation therapy in poor risk myeloid malignancies: Results of companion phase II studies.Leukemia research · 2016Trial
- Review
- CRYβB2 is a biomarker for poor prognosis and response to CDK4/6 inhibitors in breast cancer.Breast cancer research : BCR · 2026Article
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- Engineered pluronic nanomicelles containing ATRA and sodium butyrate for selective TNBC differentiation therapy.Medical oncology (Northwood, London, England) · 2025Article
- Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancer.Cell communication and signaling : CCS · 2024Review
- Nucleolin mediates SARS-CoV-2 replication and viral-induced apoptosis of host cells.Antiviral research · 2023Article
- Lipid-polymer hybrid nanoparticle with cell-distinct drug release for treatment of stemness-derived resistant tumor.Acta pharmaceutica Sinica. B · 2023Article
- Epigenetics of Thymic Epithelial Tumors.Cancers · 2023Review
- Inhibition of histone deacetylases attenuates tumor progression and improves immunotherapy in breast cancer.Frontiers in immunology · 2023Review
- ERK MAP Kinase Signaling Regulates RAR Signaling to Confer Retinoid Resistance on Breast Cancer Cells.Cancers · 2022Article
- Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice.Communications biology · 2022Article
- Histone modification and histone modification-targeted anti-cancer drugs in breast cancer: Fundamentals and beyond.Frontiers in pharmacology · 2022Review
- CRYβB2 enhances tumorigenesis through upregulation of nucleolin in triple negative breast cancer.Oncogene · 2021Article
- Breast cancer stem cells: A review of their characteristics and the agents that affect them.Molecular carcinogenesis · 2021Review
- Targeting Histone Modifications in Breast Cancer: A Precise Weapon on the Way.Frontiers in cell and developmental biology · 2021Review
- Multiple roles of HOX proteins in Metastasis: Let me count the ways.Cancer metastasis reviews · 2020Review
- Epigenetic polypharmacology: A new frontier for epi-drug discovery.Medicinal research reviews · 2020Review
- Profiling of differentially expressed genes in cadmium-induced prostate carcinogenesis.Toxicology and applied pharmacology · 2019Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Efforts to induce the differentiation of cancer stem cells through treatment with all-trans retinoic acid (ATRA) have yielded limited success, partially due to the epigenetic silencing of the retinoic acid receptor (RAR)-β The histone deacetylase inhibitor entinostat is emerging as a promising antitumor agent when added to the standard-of-care treatment for breast cancer. However, the combination of epigenetic, cellular differentiation, and chemotherapeutic approaches against triple-negative breast cancer (TNBC) has not been investigated. In this study, we found that combined treatment of TNBC xenografts with entinostat, ATRA, and doxorubicin (EAD) resulted in significant tumor regression and restoration of epigenetically silenced RAR-β expression. Entinostat and doxorubicin treatment inhibited topoisomerase II-β (TopoII-β) and relieved TopoII-β-mediated transcriptional silencing of RAR-β Notably, EAD was the most effective combination in inducing differentiation of breast tumor-initiating cells in vivo Furthermore, gene expression analysis revealed that the epithelium-specific ETS transcription factor-1 (ESE-1 or ELF3), known to regulate proliferation and differentiation, enhanced cell differentiation in response to EAD triple therapy. Finally, we demonstrate that patient-derived metastatic cells also responded to treatment with EAD. Collectively, our findings strongly suggest that entinostat potentiates doxorubicin-mediated cytotoxicity and retinoid-driven differentiation to achieve significant tumor regression in TNBC. Cancer Res; 76(7); 2013-24. ©2016 AACR.
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Registered trials
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