ArticleMolecular cancer therapeutics2014
Coordinate hyperactivation of Notch1 and Ras/MAPK pathways correlates with poor patient survival: novel therapeutic strategy for aggressive breast cancers.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- Pooled it
- Pooled it
- NOTCH2NLA gene amplification is associated with poor prognosis in breast cancer.Discover oncology · 2026Article
- AR/ERK co-targeting triggers ferroptosis via FOXC2 in triple-negative breast cancer.Science China. Life sciences · 2026Article
- Gene mutations and differentiation in laryngeal and pharyngeal squamous cell carcinoma.Discover oncology · 2025Article
- Analyzing Hedgehog pathway-related genes: insights into breast cancer tumor microenvironment and prognostic implications.Frontiers in immunology · 2025Article
- γ-Glutamylcyclotransferase is transcriptionally regulated by c-Jun and controls proliferation of glioblastoma stem cells through Notch1 levels.Cancer gene therapy · 2024Article
- Influence of copper(I) nicotinate complex on the Notch1 signaling pathway in triple negative breast cancer cell lines.Scientific reports · 2024Article
- The Intricate Notch Signaling Dynamics in Therapeutic Realms of Cancer.ACS pharmacology & translational science · 2023Review
- Sulindac sulfide as a non-immune suppressive γ-secretase modulator to target triple-negative breast cancer.Frontiers in immunology · 2023Article
- Review
- Notch Signaling in Breast Tumor Microenvironment as Mediator of Drug Resistance.International journal of molecular sciences · 2022Review
- Different Expression Levels of DLK2 Inhibit NOTCH Signaling and Inversely Modulate MDA-MB-231 Breast Cancer Tumor Growth In Vivo.International journal of molecular sciences · 2022Article
- Herbal Ingredients in the Prevention of Breast Cancer: Comprehensive Review of Potential Molecular Targets and Role of Natural Products.Oxidative medicine and cellular longevity · 2022Review
- The Role of Intracellular Trafficking of Notch Receptors in Ligand-Independent Notch Activation.Biomolecules · 2021Review
- MicroRNAs: The Link between the Metabolic Syndrome and Oncogenesis.International journal of molecular sciences · 2021Review
- Analysis of miRNA Expression in the Ileum of Broiler Chickens During Bacillus licheniformis H2 Supplementation Against Subclinical Necrotic Enteritis.Probiotics and antimicrobial proteins · 2021Article
- Notch Signalling in Breast Development and Cancer.Frontiers in cell and developmental biology · 2021Review
- Review
- Notch signaling in breast cancer: From pathway analysis to therapy.Cancer letters · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Aberrant activation of Notch and Ras pathways has been detected in breast cancers. A synergy between these two pathways has also been shown in breast cell transformation in culture. Yet, the clinical relevance of Notch-Ras cooperation in breast cancer progression remains unexplored. In this study, we show that coordinate hyperactivation of Notch1 and Ras/MAPK pathways in breast cancer patient specimens, as assessed by IHC for cleaved Notch1 and pErk1/2, respectively, correlated with early relapse to vital organs and poor overall survival. Interestingly, majority of such Notch1(high)Erk(high) cases encompassed the highly aggressive triple-negative breast cancers (TNBC), and were enriched in stem cell markers. We further show that combinatorial inhibition of Notch1 and Ras/MAPK pathways, using a novel mAb against Notch1 and a MEK inhibitor, respectively, led to a significant reduction in proliferation and survival of breast cancer cells compared with individual inhibition. Combined inhibition also abrogated sphere-forming potential, and depleted the putative cancer stem-like cell subpopulation. Most importantly, combinatorial inhibition of Notch1 and Ras/MAPK pathways completely blocked tumor growth in a panel of breast cancer xenografts, including the TNBCs. Thus, our study identifies coordinate hyperactivation of Notch1 and Ras/MAPK pathways as novel biomarkers for poor breast cancer outcome. Furthermore, based on our preclinical data, we propose combinatorial targeting of these two pathways as a treatment strategy for highly aggressive breast cancers, particularly the TNBCs that currently lack any targeted therapeutic module.
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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.