ArticleEuropean journal of cancer (Oxford, England : 1990)2015
PG545 enhances anti-cancer activity of chemotherapy in ovarian models and increases surrogate biomarkers such as VEGF in preclinical and clinical plasma samples.
Article in European journal of cancer (Oxford, England : 1990), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 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
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Drug resistance biomarkers in ovarian cancer: a bibliometric study from 2017 to 2022.Frontiers in oncology · 2024Pooled it
- The VEGF expression associated with prognosis in patients with intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.World journal of surgical oncology · 2022Pooled it
- Syndecan-1: a key player in health and disease.Immunogenetics · 2024Review
- Extracellular Matrix as a Target in Melanoma Therapy: From Hypothesis to Clinical Trials.Cells · 2024Review
- The Multiple Functions of HB-EGF in Female Reproduction and Related Cancer: Molecular Mechanisms and Targeting Strategies.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Anticancer potential of phytochemicals derived from mangrove plants: Comprehensive mechanistic insights.Food science & nutrition · 2024Review
- Endolysosomal transient receptor potential mucolipins and two-pore channels: implications for cancer immunity.Frontiers in immunology · 2024Review
- Article
- PG545 sensitizes ovarian cancer cells to PARP inhibitors through modulation of RAD51-DEK interaction.Oncogene · 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
- Underlying mechanisms and drug intervention strategies for the tumour microenvironment.Journal of experimental & clinical cancer research : CR · 2021Review
- The Role and Therapeutic Value of Syndecan-1 in Cancer Metastasis and Drug Resistance.Frontiers in cell and developmental biology · 2021Review
- Molecular Targeting of VEGF with a Suramin Fragment-DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins.Biomolecules · 2020Article
- Sulfated glycolipid PG545 induces endoplasmic reticulum stress and augments autophagic flux by enhancing anticancer chemotherapy efficacy in endometrial cancer.Biochemical pharmacology · 2020Article
- 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
- Leukocyte Heparanase: A Double-Edged Sword in Tumor Progression.Frontiers in oncology · 2019Review
- 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
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundDespite the utility of antiangiogenic drugs in ovarian cancer, efficacy remains limited due to resistance linked to alternate angiogenic pathways and metastasis. Therefore, we investigated PG545, an anti-angiogenic and anti-metastatic agent which is currently in Phase I clinical trials, using preclinical models of ovarian cancer.
methodsPG545's anti-cancer activity was investigated in vitro and in vivo as a single agent, and in combination with paclitaxel, cisplatin or carboplatin using various ovarian cancer cell lines and tumour models.
resultsPG545, alone, or in combination with chemotherapeutics, inhibited proliferation of ovarian cancer cells, demonstrating synergy with paclitaxel in A2780 cells. PG545 inhibited growth factor-mediated cell migration and reduced HB-EGF-induced phosphorylation of ERK, AKT and EGFR in vitro and significantly reduced tumour burden which was enhanced when combined with paclitaxel in an A2780 model or carboplatin in a SKOV-3 model. Moreover, in the immunocompetent ID8 model, PG545 also significantly reduced ascites in vivo. In the A2780 maintenance model, PG545 initiated with, and following paclitaxel and cisplatin treatment, significantly improved overall survival. PG545 increased plasma VEGF levels (and other targets) in preclinical models and in a small cohort of advanced cancer patients which might represent a potential biomarker of response.
conclusionOur results support clinical testing of PG545, particularly in combination with paclitaxel, as a novel therapeutic strategy for ovarian cancer.
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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.