ArticleOncotarget2016
Antitumor efficacy of the heparan sulfate mimic roneparstat (SST0001) against sarcoma models involves multi-target inhibition of receptor tyrosine kinases.
Article in Oncotarget, 2016. 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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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Towards an emerging role for anticoagulants in cancer therapy: a systematic review and meta-analysis.Frontiers in oral health · 2024Pooled it
- Targeting the heparan sulfate proteoglycan/heparanase axis as a novel therapeutic strategy to drive adipogenesis and block tumor growth of dedifferentiated liposarcoma.International journal of biological sciences · 2026Article
- Molecular pathways and therapeutic strategies in dermatofibrosarcoma protuberans (DFSP): unravelling the tumor's genetic landscape.EXCLI journal · 2024Review
- Upregulation of ERK-EGR1-heparanase axis by HDAC inhibitors provides targets for rational therapeutic intervention in synovial sarcoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Extracellular Matrices and Cancer-Associated Fibroblasts: Targets for Cancer Diagnosis and Therapy?Cancers · 2021Review
- Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics.International journal of molecular sciences · 2021Article
- Glycosaminoglycans: Carriers and Targets for Tailored Anti-Cancer Therapy.Biomolecules · 2021Review
- Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression.Frontiers in oncology · 2021Review
- Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment.International journal of molecular sciences · 2020Review
- [Heparanase promotes trans-endothelial migration of hepatocarcinoma cells by inducing apoptosis of microvascular endothelial cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Sulfated glycolipid PG545 induces endoplasmic reticulum stress and augments autophagic flux by enhancing anticancer chemotherapy efficacy in endometrial cancer.Biochemical pharmacology · 2020Article
- Non-Anticoagulant Heparins as Heparanase Inhibitors.Advances in experimental medicine and biology · 2020Review
- Heparin Binding Proteins as Therapeutic Target: An Historical Account and Current Trends.Medicines (Basel, Switzerland) · 2019Review
- Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds.iScience · 2019Review
- Heparanase: A Challenging Cancer Drug Target.Frontiers in oncology · 2019Review
- Plausibility of trophoblastic-like regulation of cancer tissue.Cancer management and research · 2019Article
- Review
- Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity.Molecules (Basel, Switzerland) · 2018Review
- Heparin Mimetics: Their Therapeutic Potential.Pharmaceuticals (Basel, Switzerland) · 2017Review
- Structure Activity Relationship of Heparin Mimicking Polymer p(SS-Polymer chemistry · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heparan sulfate (HS) mimic/heparanase inhibitor roneparstat (SST0001) shows antitumor activity in preclinical sarcoma models. We hypothesized that this 100% N-acetylated and glycol-split heparin could interfere with the functions of several receptor tyrosine kinases (RTK) coexpressed in sarcomas and activated by heparin-binding growth factors. Using a phospho-proteomic approach, we investigated the drug effects on RTK activation in human cell lines representative of different sarcoma subtypes. Inhibition of FGF, IGF, ERBB and PDGF receptors by the drug was biochemically and functionally validated. Roneparstat counteracted the autocrine loop induced by the COL1A1/PDGFB fusion oncogene, expressed in a human dermatofibrosarcoma protuberans primary culture and in NIH3T3COL1A1/PDGFB transfectants, inhibiting cell anchorage-independent growth and invasion. In addition, roneparstat inhibited the activation of cell surface PDGFR and PDGFR-associated FAK, likely contributing to the reversion of NIH3T3COL1A1/PDGFB cell transformed and pro-invasive phenotype. Biochemical and histological/immunohistochemical ex vivo analyses confirmed a reduced activation of ERBB4, EGFR, INSR, IGF1R, associated with apoptosis induction and angiogenesis inhibition in a drug-treated Ewing's sarcoma family tumor xenograft. The combination of roneparstat with irinotecan significantly improved the antitumor effect against A204 rhabdoid xenografts resulting in a high rate of complete responses and cures. These findings reveal that roneparstat exerts a multi-target inhibition of RTKs relevant in the pathobiology of different sarcoma subtypes. These effects, likely cooperating with heparanase inhibition, contribute to the antitumor efficacy of the drug. The study supports heparanase/HS axis targeting as a valuable approach in combination therapies of different sarcoma subtypes providing a preclinical rationale for clinical investigation.
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