ArticleNeuro-oncology2024
Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 21 citations in OpenAlex.
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- LCP2 mediates SUV39H1-driven cellular senescence-related chemoresistance in natural killer/T-cell lymphoma.Cell death & disease · 2026Article
- SUV family histone methyltransferases correlate with nuclear lamina remodeling and clinical outcome in cancer: integrative pan-cancer TCGA analysis and experimental evidence.Scientific reports · 2026Article
- Deciphering the tumor microenvironment and role of immunotherapy in diffuse midline glioma: A scoping review.Neuro-oncology · 2026Article
- Epigenetic mechanisms and therapeutic advances in diffuse midline glioma (Review).Oncology reports · 2026Review
- Dordaviprone: First Approval.Drugs · 2026Review
- Total Synthesis and Anticancer Study of (+)-Verticillin A.Journal of the American Chemical Society · 2025Article
- SUV39H2 is a vulnerability in glioblastoma stem cells enhanced by co-targeting SUV39H1.Epigenomics · 2025Article
- Ribosome dysregulation and intervention in age-related infertility.Cell reports. Medicine · 2025Article
- p53 regulates the expression of histone modifiers to restrict stemness and maintain differentiated luminal identity in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SUV39H1 regulates progression of pediatric diffuse high-grade gliomas through modulation of β-catenin/TCF4 levels.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Cancer and neurotransmitter receptors.Chinese medical journal · 2025Review
- Establishment of a prognostic model based on ER stress-related cell death genes and proposing a novel combination therapy in acute myeloid leukemia.Journal of translational medicine · 2025Article
- SUV39H1 maintains cancer stem cell chromatin state and properties in glioblastoma.JCI insight · 2025Article
- Targeting the Tumor Epigenetic Regulator SETDB1 for Tumor Therapy.Current cancer drug targets · 2025Review
- Review
- Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration.Biology · 2024Review
- Comprehensive gene set enrichment and variation analyses identifyComputational and structural biotechnology journal · 2024Article
- SUV39H1 epigenetically modulates the MCPIP1-AURKA signaling axis to enhance neuroblastoma tumorigenesis.Oncogene · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDiffuse intrinsic pontine gliomas (DIPG/DMG) are devastating pediatric brain tumors with extraordinarily limited treatment options and uniformly fatal prognosis. Histone H3K27M mutation is a common recurrent alteration in DIPG and disrupts epigenetic regulation. We hypothesize that genome-wide H3K27M-induced epigenetic dysregulation makes tumors vulnerable to epigenetic targeting.
methodsWe performed a screen of compounds targeting epigenetic enzymes to identify potential inhibitors for the growth of patient-derived DIPG cells. We further carried out transcriptomic and genomic landscape profiling including RNA-seq and CUT&RUN-seq as well as shRNA-mediated knockdown to assess the effects of chaetocin and SUV39H1, a target of chaetocin, on DIPG growth.
resultsHigh-throughput small-molecule screening identified an epigenetic compound chaetocin as a potent blocker of DIPG cell growth. Chaetocin treatment selectively decreased proliferation and increased apoptosis of DIPG cells and significantly extended survival in DIPG xenograft models, while restoring H3K27me3 levels. Moreover, the loss of H3K9 methyltransferase SUV39H1 inhibited DIPG cell growth. Transcriptomic and epigenomic profiling indicated that SUV39H1 loss or inhibition led to the downregulation of stemness and oncogenic networks including growth factor receptor signaling and stemness-related programs; however, D2 dopamine receptor (DRD2) signaling adaptively underwent compensatory upregulation conferring resistance. Consistently, a combination of chaetocin treatment with a DRD2 antagonist ONC201 synergistically increased the antitumor efficacy.
conclusionsOur studies reveal a therapeutic vulnerability of DIPG cells through targeting the SUV39H1-H3K9me3 pathway and compensatory signaling loops for treating this devastating disease. Combining SUV39H1-targeting chaetocin with other agents such as ONC201 may offer a new strategy for effective DIPG treatment.
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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.