ReviewFrontiers in oncology2015
Breaching the Castle Walls: Hyaluronan Depletion as a Therapeutic Approach to Cancer Therapy.
Review in Frontiers in oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 68 citations in OpenAlex.
- Engineered Extracellular Vesicles for Cancer Stem Cell Theranostics: Recent Advances and Future Perspectives.Stem cell reviews and reports · 2026Review
- KLS-3021, a multifunctional oncolytic virus, demonstrates potent early-intervention efficacy in preclinical models of prostate-confined and locally advanced prostate cancer.Frontiers in oncology · 2026Article
- Targeted Hyaluronan Degradation Enhanced Tumor Growth Inhibition in Gastrointestinal Cancer Models.Cancers · 2025Article
- Review
- Investigating the contribution of hyaluronan to the breast tumour microenvironment using multiparametric MRI and MR elastography.Molecular oncology · 2023Article
- The role of hyaluronan in renal cell carcinoma.Frontiers in immunology · 2023Review
- Adsorption of Methylene Blue on the Surface of Polymer Membrane; Dependence on the Isotopic Composition of Liquid Matrix.Polymers · 2022Article
- Article
- Intratumoral electroporation of a self-amplifying RNA expressing IL-12 induces antitumor effects in mouse models of cancer.Molecular therapy. Nucleic acids · 2022Article
- Resistance to immune checkpoint inhibitors in advanced gastro-oesophageal cancers.British journal of cancer · 2021Review
- Targeting the Stromal Pro-Tumoral Hyaluronan-CD44 Pathway in Pancreatic Cancer.International journal of molecular sciences · 2021Article
- UNIVmAb reactive albumin associated hyaladherin as a potential biomarker for colorectal cancer.Cancer biomarkers : section A of Disease markers · 2021Article
- Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy.Journal of clinical medicine · 2020Review
- Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression.International journal of molecular sciences · 2020Review
- Antifibrotic therapy to normalize the tumor microenvironment.Journal of translational medicine · 2020Review
- Computational modeling of therapy on pancreatic cancer in its early stages.Biomechanics and modeling in mechanobiology · 2020Article
- Towards extracellular matrix normalization for improved treatment of solid tumors.Theranostics · 2020Review
- ENHANZEDrug delivery · 2019Review
- The growth of a xenograft breast cancer tumor model with engineered hyaluronan-accumulating stroma is dependent on hyaluronan and independent of CD44.Oncotarget · 2019Article
- Optimizing pharmacokinetics of intravesical chemotherapy for bladder cancer.Nature reviews. Urology · 2019Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyaluronan (HA) has many functions in the extracellular milieu of normal and diseased tissues. Disease-associated HA accumulation has been shown to predict a worsened prognosis in cancer patients, with tumors having a high-extracellular HA content (HA-high) being more aggressive than their HA-low counterparts. HA-high tumor aggressiveness is derived from the specialized biomechanical and molecular properties of the HA-based assembly of HA binding proteins and the growth-promoting factors that accumulate in it. Biophysical characteristics of an HA-high tumor microenvironment include high tumor interstitial pressure, compression of tumor vasculature, and resulting tumor hypoxia. Within the tumor cell membrane, HA receptors, primarily CD44 and RHAMM, anchor the HA-high extracellular network. HA-CD44 association on the tumor cell surface enhances receptor tyrosine kinase activity to drive tumor progression and treatment resistance. Together, malignant cells in this HA-high matrix may evolve dependency on it for growth. This yields the hypothesis that depleting HA in HA-high tumors may be associated with a therapeutic benefit. A pegylated form of recombinant human hyaluronidase PH20 (PEGPH20) has been deployed as a potential cancer therapeutic in HA-high tumors. PEGPH20 can collapse this matrix by degrading the HA-assembled tumor extracellular framework, leading to tumor growth inhibition, preferentially in HA-high tumors. Enzymatic depletion of HA by PEGPH20 results in re-expansion of the tumor vasculature, reduction in tumor hypoxia, and increased penetration of therapeutic molecules into the tumor. Finally, HA-depletion results in reduced signaling via CD44/RHAMM. Taken together, HA-depletion strategies accomplish their antitumor effects by multiple mechanisms that include targeting both biophysical and molecular signaling pathways. Ongoing clinical trials are examining the potential of PEGPH20 in combination with partner therapeutics in several cancers.
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