ArticleNeuro-oncology2019
A large-scale drug screen identifies selective inhibitors of class I HDACs as a potential therapeutic option for SHH medulloblastoma.
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 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Macrophage-Centric Phenotypic Screening Identifies Tetrazolone-Based HDAC6 Inhibitors That Reprogram the Tumor Immune Microenvironment and Improve Immune Checkpoint Blockade.Journal of medicinal chemistry · 2026Article
- TRIM21 promotes astrocyte-mediated neuroinflammation in experimental autoimmune encephalomyelitis by stabilizing RGMa via K33-linked ubiquitination.Journal of neuroinflammation · 2026Article
- Medulloblastoma in Adolescents and Young Adults: Molecular Subgroups, Prognostic Biomarkers, and Age-Specific Therapeutic Challenges.Current issues in molecular biology · 2026Review
- Central nervous system distributional kinetics of selected histone deacetylase inhibitors.The Journal of pharmacology and experimental therapeutics · 2025Article
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- Genome-wide CRISPR-Cas9 knockout screens identify DNMT1 as a druggable dependency in sonic hedgehog medulloblastoma.Acta neuropathologica communications · 2024Article
- Mechanistic insights into medulloblastoma relapse.Pharmacology & therapeutics · 2024Review
- Advances in targeting histone deacetylase for treatment of solid tumors.Journal of hematology & oncology · 2024Review
- Central Nervous System Distribution of Panobinostat in Preclinical Models to Guide Dosing for Pediatric Brain Tumors.The Journal of pharmacology and experimental therapeutics · 2023Article
- Quisinostat is a brain-penetrant radiosensitizer in glioblastoma.JCI insight · 2023Article
- Epigenetics and immune cells in medulloblastoma.Frontiers in genetics · 2023Review
- Multiprotein GLI Transcriptional Complexes as Therapeutic Targets in Cancer.Life (Basel, Switzerland) · 2022Review
- Medulloblastoma in the Modern Era: Review of Contemporary Trials, Molecular Advances, and Updates in Management.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Cancer stem cells, not bulk tumor cells, determine mechanisms of resistance to SMO inhibitors.Cancer research communications · 2022Article
- Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance.International journal of molecular sciences · 2022Review
- Small Molecule Inhibitors in Adult High-Grade Glioma: From the Past to the Future.Frontiers in oncology · 2022Review
- Nonredundant, isoform-specific roles of HDAC1 in glioma stem cells.JCI insight · 2021Article
- Development of Randomized Trials in Adults with Medulloblastoma-The Example of EORTC 1634-BTG/NOA-23.Cancers · 2021Review
- Epigenetic-Based Therapy-A Prospective Chance for Medulloblastoma Patients' Recovery.International journal of molecular sciences · 2021Review
- Biological Role of MYCN in Medulloblastoma: Novel Therapeutic Opportunities and Challenges Ahead.Frontiers in oncology · 2021Review
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundMedulloblastoma (MB) is one of the most frequent malignant brain tumors of children, and a large set of these tumors is characterized by aberrant activation of the sonic hedgehog (SHH) pathway. While some tumors initially respond to inhibition of the SHH pathway component Smoothened (SMO), tumors ultimately recur due to downstream resistance mechanisms, indicating a need for novel therapeutic options.
methodsHere we performed a targeted small-molecule screen on a stable, SHH-dependent murine MB cell line (SMB21). Comprehensive isotype profiling of histone deacetylase (HDAC) inhibitors was performed, and effects of HDAC inhibition were evaluated in cell lines both sensitive and resistant to SMO inhibition. Lastly, distinct mouse models of SHH MB were used to demonstrate pharmacologic efficacy in vivo.
resultsA subset of the HDAC inhibitors tested significantly inhibit tumor growth of SMB21 cells by preventing SHH pathway activation. Isotype profiling of HDAC inhibitors, together with genetic approaches suggested that concerted inhibition of multiple class I HDACs is necessary to achieve pathway inhibition. Of note, class I HDAC inhibitors were also efficacious in suppressing growth of diverse SMO inhibitor‒resistant clones of SMB21 cells. Finally, we show that the novel HDAC inhibitor quisinostat targets multiple class I HDACs, is well tolerated in mouse models, and robustly inhibits growth of SHH MB cells in vivo as well as in vitro.
conclusionsOur data provide strong evidence that quisinostat or other class I HDAC inhibitors might be therapeutically useful for patients with SHH MB, including those resistant to SMO inhibition.
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