ArticlePloS one2012
PG545, a heparan sulfate mimetic, reduces heparanase expression in vivo, blocks spontaneous metastases and enhances overall survival in the 4T1 breast carcinoma model.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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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
41 citing papers in PubMed, 58 citations in OpenAlex.
- Investigation into the binding domains of platelet factor 4 unlocks new avenues for the design and synthesis of selective sulfated pseudo-tetrasaccharide aminoglycoside ligands.European journal of medicinal chemistry · 2025Article
- Heparin, Heparin-like Molecules, and Heparin Mimetics in Breast Cancer: A Concise Review.Biomolecules · 2025Review
- PG545 sensitizes ovarian cancer cells to PARP inhibitors through modulation of RAD51-DEK interaction.Oncogene · 2023Article
- Targeting Breast Cancer: The Familiar, the Emerging, and the Uncharted Territories.Biomolecules · 2023Review
- Investigating the Role of Heparanase in Breast Cancer Development Utilising the MMTV-PyMT Murine Model of Mammary Carcinoma.Cancers · 2023Article
- Heparan sulfate proteoglycans in cancer: Pathogenesis and therapeutic potential.Advances in cancer research · 2023Article
- Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumab in subjects with microsatellite-stable metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma and other solid tumors.Journal for immunotherapy of cancer · 2023Article
- Review
- Heparin-Superparamagnetic Iron Oxide Nanoparticles for Theranostic Applications.Molecules (Basel, Switzerland) · 2022Article
- Heparan sulfate proteoglycans as targets for cancer therapy: a review.Cancer biology & therapy · 2020Review
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment.International journal of molecular sciences · 2020Review
- The Heparan Sulfate Mimetic PG545 Modulates T Cell Responses and Prevents Delayed-Type Hypersensitivity.Frontiers in immunology · 2020Article
- Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds.iScience · 2019Review
- Cancer Metastasis: The Role of the Extracellular Matrix and the Heparan Sulfate Proteoglycan Perlecan.Frontiers in oncology · 2019Review
- HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist.Oxidative medicine and cellular longevity · 2019Article
- Leukocyte Heparanase: A Double-Edged Sword in Tumor Progression.Frontiers in oncology · 2019Review
- Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity.Molecules (Basel, Switzerland) · 2018Review
- Immunomodulatory activities of pixatimod: emerging nonclinical and clinical data, and its potential utility in combination with PD-1 inhibitors.Journal for immunotherapy of cancer · 2018Article
- Establishment of a murine breast tumor model by subcutaneous or orthotopic implantation.Oncology letters · 2018Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PG545 is a clinically relevant heparan sulfate (HS) mimetic which, in addition to possessing anti-angiogenic properties, also acts as a heparanase inhibitor which may differentiate its mechanism(s) of action from approved angiogenesis inhibitors. The degradation of HS by heparanase has been strongly implicated in cell dissemination and the metastatic process. Thus, the anti-metastatic activity of PG545 has been linked to the enzymatic function of heparanase - the only endoglycosidase known to cleave HS, an important component of the extracellular matrix (ECM) which represents a potential avenue for therapeutic intervention for certain metastatic cancer indications. Recent concerns raised about the paucity of overall survival as an endpoint in mouse models of clinically relevant metastasis led us to examine the effect of PG545 on the progression of both primary tumor growth and the spontaneously metastasizing disease in the 4T1 syngeneic breast carcinoma model in a non-surgical and surgical (mastectomy) setting. PG545 significantly inhibited primary tumor growth but importantly also inhibited lung metastasis in treated mice, an effect not observed with the tyrosine kinase inhibitor sorafenib. Importantly, PG545 significantly enhanced overall survival compared to vehicle control and the sorafenib group, suggesting PG545's inhibitory effect on heparanase is indeed a critical attribute to induce anti-metastatic activity. In addition to blocking a common angiogenic signalling pathway in tumor cells, the expression of heparanase in the primary tumor and lung was also significantly reduced by PG545 treatment. These results support the ongoing development of PG545 and highlight the potential utility in metastatic disease settings.
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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.