ArticleJournal of experimental & clinical cancer research : CR2021
PEGylated recombinant human hyaluronidase (PEGPH20) pre-treatment improves intra-tumour distribution and efficacy of paclitaxel in preclinical models.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 53 citations in OpenAlex.
- Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer: MORPHEUS Phase Ib/II Umbrella Randomized Study Platform.The oncologist · 2023Trial
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- Engineering Mesenchymal Stem Cells with Nanomaterials for Tumor Microenvironment Regulation and Precision Therapy.Tissue engineering and regenerative medicine · 2026Review
- From permeation enhancer to therapeutic enabler: Advances, applications, and translational perspectives in hyaluronidase-based drug delivery.Materials today. Bio · 2026Review
- Two Worlds, One Battle: How Bacteria and Malignancies Converge on Drug Resistance.International journal of molecular sciences · 2026Review
- Cancer-associated fibroblast targeting therapies as a tool to enhance responses to radiotherapy and immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Review
- Salmonella typhimurium co-expressing cytolysin A and hyaluronidase suppresses tumor growth and metastasis.Cell death discovery · 2026Article
- Current Status of Research on Losartan in Tumour Therapy.Journal of cellular and molecular medicine · 2026Review
- Recent advances in nanoparticles-based sonodynamic and immune checkpoint blockade synergistic therapy for pancreatic ductal adenocarcinoma.Materials today. Bio · 2025Review
- Drug resistance in cancer: molecular mechanisms and emerging treatment strategies.Molecular biomedicine · 2025Review
- Targeted Hyaluronan Degradation Enhanced Tumor Growth Inhibition in Gastrointestinal Cancer Models.Cancers · 2025Article
- Cancer Metastasis: Therapeutic Challenges and Opportunities.Medical oncology (Northwood, London, England) · 2025Review
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Three-dimensional traction technology and its application in mechanomedicine.Mechanobiology in medicine · 2025Review
- Systematic profiling of cancer-fibroblast interactions reveals drug combinations in ovarian cancer.Molecular oncology · 2025Article
- Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy.Journal of hematology & oncology · 2025Review
- Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells.The Journal of clinical investigation · 2025Article
- Tumor microenvironment as niche constructed by cancer stem cells: Breaking the ecosystem to combat cancer.Journal of advanced research · 2025Review
- Resistance signatures to oncolytic vesiculoviruses in pancreatic ductal adenocarcinoma.Molecular therapy. Oncology · 2025Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundScarce drug penetration in solid tumours is one of the possible causes of the limited efficacy of chemotherapy and is related to the altered tumour microenvironment. The abnormal tumour extracellular matrix (ECM) together with abnormal blood and lymphatic vessels, reactive stroma and inflammation all affect the uptake, distribution and efficacy of anticancer drugs.
methodsWe investigated the effect of PEGylated recombinant human hyaluronidase PH20 (PEGPH20) pre-treatment in degrading hyaluronan (hyaluronic acid; HA), one of the main components of the ECM, to improve the delivery of antitumor drugs and increase their therapeutic efficacy. The antitumor activity of paclitaxel (PTX) in HA synthase 3-overexpressing and wild-type SKOV3 ovarian cancer model and in the BxPC3 pancreas xenograft tumour model, was evaluated by monitoring tumour growth with or without PEGPH20 pre-treatment. Pharmacokinetics and tumour penetration of PTX were assessed by HPLC and mass spectrometry imaging analysis in the same tumour models. Tumour tissue architecture and HA deposition were analysed by histochemistry.
resultsPre-treatment with PEGPH20 modified tumour tissue architecture and improved the antitumor activity of paclitaxel in the SKOV3/HAS3 tumour model, favouring its accumulation and more homogeneous intra-tumour distribution, as assessed by quantitative and qualitative analysis. PEGPH20 also reduced HA content influencing, though less markedly, PTX distribution and antitumor activity in the BxPC3 tumour model.
conclusionRemodelling the stroma of HA-rich tumours by depletion of HA with PEGPH20 pre-treatment, is a potentially successful strategy to improve the intra-tumour distribution of anticancer drugs, increasing their therapeutic efficacy, without increasing toxicity.
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