ArticleOncogene2019
Eicosapentaenoic acid in combination with EPHA2 inhibition shows efficacy in preclinical models of triple-negative breast cancer by disrupting cellular cholesterol efflux.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- The Effects of Omega-3 Polyunsaturated Fatty Acids on Breast Cancer as a Preventive Measure or as an Adjunct to Conventional Treatments.Nutrients · 2023Pooled it
- Multiomics identifies a cholesterol-TFEB-PLD3-TLR9 axis driving immunosuppressive tumor-associated macrophage polarization in esophageal squamous cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Carrier-Free Nanocombo-Sensitized Photoimmunotherapy via Activation of α2-Adrenergic Receptors.ACS applied materials & interfaces · 2025Article
- Eicosapentaenoic Acid Triggers Phosphatidylserine Externalization in the Erythrocyte Membrane through Calcium Signaling and Anticholinesterase Activity.Physiological research · 2024Article
- EphA2 blockage ALW-II-41-27 alleviates atherosclerosis by remodeling gut microbiota to regulate bile acid metabolism.NPJ biofilms and microbiomes · 2024Article
- Erythropoietin-induced hepatocyte receptor A2 regulates effect of pyroptosis on gastrointestinal colorectal cancer occurrence and metastasis resistance.World journal of gastrointestinal oncology · 2024Review
- Targeting Interleukin-13 Receptor α2 and EphA2 in Aggressive Breast Cancer Subtypes with Special References to Chimeric Antigen Receptor T-Cell Therapy.International journal of molecular sciences · 2024Review
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- The value of plasma omega-3 polyunsaturated fatty acids in predicting the response and prognosis of cervical squamous cell carcinoma patients to concurrent chemoradiotherapy.Frontiers in pharmacology · 2024Article
- Increased Expression of the ABCA1 and ABCA3 Transporter Genes is Associated with Cisplatin Resistance in Breast Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- The Involvement of Polyunsaturated Fatty Acids in Apoptosis Mechanisms and Their Implications in Cancer.International journal of molecular sciences · 2023Review
- Eph Receptors in Cancer.Biomedicines · 2023Review
- Article
- EPH/Ephrin-Targeting Treatment in Breast Cancer: A New Chapter in Breast Cancer Therapy.International journal of molecular sciences · 2022Review
- Suppression of the ABCA1 Cholesterol Transporter Impairs the Growth and Migration of Epithelial Ovarian Cancer.Cancers · 2022Article
- Alteration of cholesterol distribution at the plasma membrane of cancer cells: From evidence to pathophysiological implication and promising therapy strategy.Frontiers in physiology · 2022Review
- Mechanistic Insights Delineating the Role of Cholesterol in Epithelial Mesenchymal Transition and Drug Resistance in Cancer.Frontiers in cell and developmental biology · 2021Review
- EPHA mutation as a predictor of immunotherapeutic efficacy in lung adenocarcinoma.Journal for immunotherapy of cancer · 2020Article
- High-throughput, Label-Free Quantitative Proteomic Studies of the Anticancer Effects of Electrical Pulses with Turmeric Silver Nanoparticles: an in vitro Model Study.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype, currently lacks effective targeted therapy options. Eicosapentaenoic acid (EPA), an omega-3 fatty acid and constituent of fish oil, is a common supplement with anti-inflammatory properties. Although it is not a mainstream treatment, several preclinical studies have demonstrated that EPA exerts anti-tumor activity in breast cancer. However, against solid tumors, EPA as a monotherapy is clinically ineffective; thus, we sought to develop a novel targeted drug combination to bolster its therapeutic action against TNBC. Using a high-throughput functional siRNA screen, we identified Ephrin type-A receptor 2 (EPHA2), an oncogenic cell-surface receptor tyrosine kinase, as a therapeutic target that sensitizes TNBC cells to EPA. EPHA2 expression was uniquely elevated in TNBC cell lines and patient tumors. In independent functional expression studies in TNBC models, EPHA2 gene-silencing combined with EPA significantly reduced cell growth and enhanced apoptosis compared with monotherapies, both in vitro and in vivo. EPHA2-specific inhibitors similarly enhanced the therapeutic action of EPA. Finally, we identified that therapy-mediated apoptosis was attributed to a lethal increase in cancer cell membrane polarity due to ABCA1 inhibition and subsequent dysregulation of cholesterol homeostasis. This study provides new molecular and preclinical evidence to support a clinical evaluation of EPA combined with EPHA2 inhibition in patients with 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.