ArticleThe Journal of clinical investigation2019
Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A2.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 5 of them syntheses that pooled it.
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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
138 citing papers in PubMed, 5 syntheses or guidelines pooled it, 218 citations in OpenAlex.
- The Anti-Metastatic Role of Aspirin in Cancer: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Global hotspots and trends in pre-metastatic niche research: a bibliometric analysis(2005-2024).Frontiers in immunology · 2025Pooled it
- Different antithrombotic strategies to prevent cardiovascular complications in Kawasaki patients: a systematic review and meta-analysis.BMC pediatrics · 2024Pooled it
- Aspirin Use and Survival Among Patients With Breast Cancer: A Systematic Review and Meta-Analysis.The oncologist · 2024Pooled it
- Risk mapping of lung cancer: a comprehensive appraisal of published meta-analyses incorporating Mendelian randomization studies.Journal of cancer research and clinical oncology · 2023Pooled it
- Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial.British journal of cancer · 2023Trial
- Inflammation and carcinogenesis: molecular targets and small-molecule intervention strategies.Journal of enzyme inhibition and medicinal chemistry · 2026Review
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- Platelets as regulators of anti-tumor immunity: mechanisms and clinical implications.Cancer metastasis reviews · 2026Review
- P2Y12-P-selectin-mediated platelet activation in a murine model of dengue-associated thrombocytopenia.EBioMedicine · 2026Article
- Tumoral extracellular vesicles and particles reprogram interstitial macrophages in the lung to promote vascular permeability and metastasis.Nature cancer · 2026Article
- Tumor-platelet cross talk in cancer: mechanisms, thrombotic risk, and translational opportunities.Blood advances · 2026Review
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- TBXA2R activates ERMs to drive motility, invasion, and metastatic colonization of TNBC cells.Life science alliance · 2026Article
- Platelet-neutrophil cooperation in cancer: mechanisms of metastatic niche formation and implications for prognostic stratification and therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Engineering platelets as cancer therapeutics.Nature reviews. Clinical oncology · 2026Review
- Nature-inspired confined cascade enzyme nanoreactors for targeted atherosclerosis therapy.Signal transduction and targeted therapy · 2026Article
- Study on the mechanism of hUCMSCs-derived 3D exosome combined with HAMA microneedles in the treatment of deep second-degree burns.Bioactive materials · 2026Article
- Drug re-purposing to improve outcomes in the management of prostate cancer - aims, outcome measures and design of current phase III trials.BMC pharmacology & toxicology · 2026Review
- Canadine protects against doxorubicin-induced cardiac and brain injury by inhibiting Oxidative stress.BMC pharmacology & toxicology · 2026Article
78 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Because metastasis is associated with the majority of cancer-related deaths, its prevention is a clinical aspiration. Prostanoids are a large family of bioactive lipids derived from the activity of cyclooxygenase-1 (COX-1) and COX-2. Aspirin impairs the biosynthesis of all prostanoids through the irreversible inhibition of both COX isoforms. Long-term administration of aspirin leads to reduced distant metastases in murine models and clinical trials, but the COX isoform, downstream prostanoid, and cell compartment responsible for this effect are yet to be determined. Here, we have shown that aspirin dramatically reduced lung metastasis through inhibition of COX-1 while the cancer cells remained intravascular and that inhibition of platelet COX-1 alone was sufficient to impair metastasis. Thromboxane A2 (TXA2) was the prostanoid product of COX-1 responsible for this antimetastatic effect. Inhibition of the COX-1/TXA2 pathway in platelets decreased aggregation of platelets on tumor cells, endothelial activation, tumor cell adhesion to the endothelium, and recruitment of metastasis-promoting monocytes/macrophages, and diminished the formation of a premetastatic niche. Thus, platelet-derived TXA2 orchestrates the generation of a favorable intravascular metastatic niche that promotes tumor cell seeding and identifies COX-1/TXA2 signaling as a target for the prevention of metastasis.
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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.