ArticleNeuro-oncology2019
Gene therapy with apoptosis-associated speck-like protein, a newly described schwannoma tumor suppressor, inhibits schwannoma growth in vivo.
Article in Neuro-oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis 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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Pyroptosis in Peripheral Neuropathy: From Molecular Mechanisms to Therapeutic Targeting.CNS neuroscience & therapeutics · 2026Pooled it
- Deletion of themBio · 2026Article
- Pathologic and Therapeutic Schwann Cells.Cells · 2025Review
- Gene therapy and genome-editing for schwannoma in NF2-related schwannomatosis: current understanding and future directions.Journal of neuro-oncology · 2025Review
- The evolving landscape of NF gene therapy: Hurdles and opportunities.Molecular therapy. Nucleic acids · 2025Review
- WWC proteins-mediated compensatory mechanism restricts schwannomatosis driven byScience advances · 2025Article
- Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.Current issues in molecular biology · 2024Review
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Gene Therapy for Neurofibromatosis Type 2-Related Schwannomatosis: Recent Progress, Challenges, and Future Directions.Oncology and therapy · 2024Review
- Article
- Culture of attenuatedHuman vaccines & immunotherapeutics · 2023Article
- The genetic landscape and possible therapeutics of neurofibromatosis type 2.Cancer cell international · 2023Review
- Tumor Biology and Microenvironment of Vestibular Schwannoma-Relation to Tumor Growth and Hearing Loss.Biomedicines · 2022Review
- Gene replacement therapy in a schwannoma mouse model of neurofibromatosis type 2.Molecular therapy. Methods & clinical development · 2022Article
- Intratumoral injection of schwannoma with attenuatedProceedings of the National Academy of Sciences of the United States of America · 2022Article
- A Critical Overview of Targeted Therapies for Vestibular Schwannoma.International journal of molecular sciences · 2022Review
- Schwannoma Gene Therapy via Adeno-Associated Viral Vector Delivery of Apoptosis-Associated Speck-like Protein Containing CARD (ASC): Preclinical Efficacy and Safety.International journal of molecular sciences · 2022Article
- Molecular Features of a Primary Transmural Tracheal Schwannoma: Clinical Experience and Review of the Literature.Cancer management and research · 2022Article
- Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy.International journal of molecular sciences · 2021Review
- The role of mRNA in the development, diagnosis, treatment and prognosis of neural tumors.Molecular cancer · 2021Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundWe evaluated apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) as a schwannoma tumor suppressor and explored its utilization in a schwannoma gene therapy strategy that may be translated to clinical use.
methodsASC protein expression and mRNA level were assessed in human schwannoma by immunohistochemistry and quantitative PCR, respectively. Methylation- specific PCR was used to assess ASC promoter methylation. The effect of ASC overexpression in schwannoma cells was evaluated through ATP-based viability, lactate dehydrogenase release, and apoptosis staining. Western blotting and colorimetric assay were used to test the effect of ASC overexpression on endogenous pro-apoptotic pathways. Bioluminescence imaging, behavioral testing, and immunohistochemistry in human xenograft and murine allograft schwannoma models were used to examine the efficacy and toxicity of intratumoral injection of adeno-associated virus (AAV) vector encoding ASC.
resultsASC expression was suppressed via promoter methylation in over 80% of the human schwannomas tested. ASC overexpression in schwannoma cells results in cell death and is associated with activation of endogenous caspase-9, caspase-3, and upregulation of BH3 interacting-domain death agonist. In a human xenograft schwannoma model, AAV1-mediated ASC delivery reduced tumor growth and resolved tumor-associated pain without detectable toxicity, and tumor control was associated with reduced Ki67 mitotic index and increased tumor-cell apoptosis. Efficacy of this schwannoma gene therapy strategy was confirmed in a murine schwannoma model.
conclusionWe have identified ASC as a putative schwannoma tumor suppressor with high potential clinical utility for schwannoma gene therapy and generated a vector that treats schwannomas via a novel mechanism that does not overlap with current treatments.
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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.