ArticleCancer biology & therapy2015
Thrombin inhibition and cyclophosphamide synergistically block tumor progression and metastasis.
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Towards an emerging role for anticoagulants in cancer therapy: a systematic review and meta-analysis.Frontiers in oral health · 2024Pooled it
- Platelets as regulators of anti-tumor immunity: mechanisms and clinical implications.Cancer metastasis reviews · 2026Review
- Fully Synthetic Non-Carbohydrate Heparin Mimetics-Perspectives for Therapeutic Anticoagulation and Beyond?Archiv der Pharmazie · 2026Review
- Anticoagulants beyond coagulation: a narrative review of cardiovascular effects.Cardiovascular research · 2026Review
- Bidirectional regulatory mechanisms and therapeutic prospects of tumor hypercoagulable state and immunosuppressive tumor microenvironment.Oncology reviews · 2026Review
- Emerging roles of haemostatic proteins as markers of disease progression and prognosis in breast cancer.Exploration of targeted anti-tumor therapy · 2026Review
- Inhibition of FXa could be a novel therapeutic target associated with hypoxia-associated tumor behavior?Discover oncology · 2025Article
- Antitumor Effects and the Potential Mechanism of 10-HDA against SU-DHL-2 Cells.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Anti-Inflammatory and Anticancer Effects of Anticoagulant Therapy in Patients with Malignancy.Life (Basel, Switzerland) · 2023Review
- Reprogramming the immunosuppressive tumor microenvironment: exploiting angiogenesis and thrombosis to enhance immunotherapy.Frontiers in immunology · 2023Review
- Commonly Prescribed Anticoagulants Exert Anticancer Effects in Oral Squamous Cell Carcinoma Cells In Vitro.Biology · 2022Article
- Direct Thrombin Inhibitor Dabigatran Compromises Pulmonary Endothelial Integrity in a Murine Model of Breast Cancer Metastasis to the Lungs; the Role of Platelets and Inflammation-Associated Haemostasis.Frontiers in pharmacology · 2022Article
- Review
- Article
- Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-β.Science translational medicine · 2020Article
- The direct oral anticoagulants rivaroxaban and dabigatran do not inhibit orthotopic growth and metastasis of human breast cancer in mice.Journal of thrombosis and haemostasis : JTH · 2019Article
- Review
- Protease-activated receptor 1 activation enhances doxorubicin-induced cardiotoxicity.Journal of molecular and cellular cardiology · 2018Article
- Targeting Platelets for the Treatment of Cancer.Cancers · 2017Review
- Antiplatelet agents for cancer treatment: a real perspective or just an echo from the past?Cancer metastasis reviews · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer is often associated with an increased risk of thrombotic events which are exacerbated by treatment with chemotherapeutics such as cyclosphosphamide (CP). Evidence suggests that thrombin can stimulate tumor progression via formation of fibrin and activation of protease-activated receptors (PARs) and platelets. We examined the effect of co-treatment with CP and dabigatran etexilate, a direct inhibitor of thrombin, using the murine orthotopic 4T1 tumor model. Mice receiving co-treatment with both low dose CP and dabigatran etexilate had significantly smaller mammary tumors and fewer lung metastases than mice treated with CP or dabigratran etexilate alone. Co-treatment with dabigatran etexilate and low dose CP also significantly decreased the number of arginase(+)Gr-1(+)CD11b(+) myeloid derived suppressor cells as well as levels of TGF-β in spleens from tumor bearing mice. 4T1 tumors express procoagulant tissue factor (TF) and spontaneously release TF(+) microparticles which are potent procoagulant factors that promote thrombin generation. Treatment with dabigatran etexilate alone prevented tumor-induced increases in circulating TF(+) microparticles and also decreased the numbers of tumor-induced activated platelets by 40%. These results show that co-treatment with dabigatran etexilate and CP synergistically inhibits growth and metastasis of mammary tumors, suggesting that oral administration of the thrombin inhibitor dabigatran etexilate may be beneficial in not only preventing thrombotic events in cancer patients but also in treating malignant tumors themselves.
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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.