ArticleBreast cancer research : BCR2015
Inhibition of iNOS as a novel effective targeted therapy against triple-negative breast cancer.
Article in Breast cancer research : BCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05660083 (Phase II Trial of Alpelisib With iNOS Inhibitor and Nab-paclitaxel in Patients With HER2 Negative Metastatic or Locally Advanced Metaplastic Breast Cancer), which is not on this map. Cited by 129 papers.
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.
Phase II Trial of Alpelisib With iNOS Inhibitor and Nab-paclitaxel in Patients With HER2 Negative Metastatic or Locally Advanced Metaplastic Breast Cancer (MpBC)
Who cites it
129 citing papers in PubMed, 220 citations in OpenAlex.
- A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer.Breast cancer research : BCR · 2020Trial
- IFN-γ-driven iNOS induction in macrophages mediates CAR T cell resistance in B cell lymphoma.Nature communications · 2026Article
- NOS2 and COX2 impact the spatial landscape of CD8Redox biology · 2026Review
- Evaluating the Efficacy of Polyphenol-Enriched Plant Extracts and Pathway Modulators in the Bone Marrow to Suppress Breast Cancer Progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Propionate metabolism is dysregulated in non-small cell lung cancer patients and EGFR-mutant drug-tolerant persister cells.Scientific reports · 2026Article
- S-nitrosylated COX-2 is a microenvironment-regulated breast cancer cell biomarker of mesenchymal phenotypes.Experimental cell research · 2026Article
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- NO/iNOS axis impact on glioma stem cells and temozolomide resistance.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Recent advances in the investigation of the regulatory network underlying reactive nitrogen species-mediated tumorigenesis: molecular mechanisms and targeted therapeutic strategies.Redox report : communications in free radical research · 2025Review
- Neutrophil Dynamics Contribute to Disease Progression and Poor Survival in Pancreatic Cancer.Cancers · 2025Article
- Propionate metabolism dysregulation promotes drug-tolerant persister cell survival in non-small cell lung cancer.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of iNOS reduced cerebral vasoconstriction from chronic cocaine and enhanced angiogenesis in the prefrontal cortex.Brain research bulletin · 2025Article
- Developments in the connection between epithelial‑mesenchymal transition and endoplasmic reticulum stress (Review).International journal of molecular medicine · 2025Review
- The Role of Nitric Oxide in Cancer Treatment: Ally or Foe?Molecules (Basel, Switzerland) · 2025Review
- Inducible nitric oxide synthase (iNOS): More than an inducible enzyme? Rethinking the classification of NOS isoforms.Pharmacological research · 2025Review
- Real-time nitric oxide detection in cytokine stimulated cancer cells and macrophages.Nitric oxide : biology and chemistry · 2025Article
- L-arginine dependence of breast cancer - molecular subtypes matter.BMC cancer · 2025Article
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- Targeting the Molecules in EMT: A Potential Therapeutic Opportunity in Breast Cancer.Current molecular medicine · 2025Review
- Plant metabolites and functional foods in metastatic breast cancer: a supportive strategy for management.Frontiers in pharmacology · 2025Review
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
introductionTriple-negative breast cancer (TNBC) is an aggressive form of breast cancer with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) is associated with poor survival in patients with breast cancer by increasing tumor aggressiveness. This work aimed to investigate the potential of iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor initiation and metastasis through modulation of epithelial-mesenchymal transition (EMT)-inducing factors.
methodsiNOS protein levels were determined in 83 human TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere-forming efficiency, migration, and EMT transcription factors were assessed in vitro after iNOS inhibition. Endogenous iNOS targeting was evaluated as a potential therapy in TNBC mouse models.
resultsHigh endogenous iNOS expression was associated with worse prognosis in patients with TNBC by gene expression as well as immunohistochemical analysis. Selective iNOS (1400 W) and pan-NOS (L-NMMA and L-NAME) inhibitors diminished cell proliferation, cancer stem cell self-renewal, and cell migration in vitro, together with inhibition of EMT transcription factors (Snail, Slug, Twist1, and Zeb1). Impairment of hypoxia-inducible factor 1α, endoplasmic reticulum stress (IRE1α/XBP1), and the crosstalk between activating transcription factor 3/activating transcription factor 4 and transforming growth factor β was observed. iNOS inhibition significantly reduced tumor growth, the number of lung metastases, tumor initiation, and self-renewal.
conclusionsConsidering the effectiveness of L-NMMA in decreasing tumor growth and enhancing survival rate in TNBC, we propose a targeted therapeutic clinical trial by re-purposing the pan-NOS inhibitor L-NMMA, which has been extensively investigated for cardiogenic shock as an anti-cancer therapeutic.
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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.