ArticleCancer discovery2024
Perivascular NOTCH3+ Stem Cells Drive Meningioma Tumorigenesis and Resistance to Radiotherapy.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Cell atlas of the developing human meninges reveals a dura-like nature of meningiomas.Nature cell biology · 2026Article
- Modeling meningioma in vitro in the omics era.Human cell · 2026Review
- Leveraging single-cell and spatial omics for brain tumour insights to improve therapeutic strategies.Molecular brain · 2026Review
- A proteogenomic RNA processing mechanism drives sex differences in meningioma.Research square · 2026Article
- Current evidence on the cell of origin of meningiomas disputes the arachnoid cap cell dogma.Acta neurochirurgica · 2026Review
- Novel NOTCH3 alteration expanding the molecular spectrum of pericytic tumours: report of two cases.Histopathology · 2026Article
- Review
- STING activation induces cytotoxic and immune responses in meningiomas via inflammatory cell death pathways.Nature communications · 2026Article
- MCell death & disease · 2026Article
- Phase-Change Assembling Nanostructures Synergistically Potentiate Tumor Radiosensitivity by Reducing the Stemness of Cancer Stem-Like Cells.Exploration (Beijing, China) · 2026Article
- Distant Metastases of an Atypical Meningioma 14 Years Later After Primary Tumor Resection: A Case Report and Review of the Literature.Case reports in pathology · 2026Article
- NOTCH3 attenuates cytotoxicity via RBPJ-dependent PVR upregulation to influence immunotherapy outcomes in colorectal cancer.Frontiers in immunology · 2026Article
- NOTCH3 drives fatty acid oxidation and ferroptosis resistance in aggressive meningiomas.Journal of neuro-oncology · 2025Article
- Single-cell analysis reveals a longitudinal trajectory of meningioma evolution and heterogeneity.Nature communications · 2025Article
- Cancer stem cells: Bridging microenvironmental interactions and clinical therapy.Clinical and translational medicine · 2025Review
- Cas9 Mouse Model of Skull Base Meningioma Driven by Combinational Gene Inactivation in Meningeal Cells.CNS neuroscience & therapeutics · 2025Article
- Meningeal solitary fibrous tumor cell states phenocopy cerebral vascular development and homeostasis.Neuro-oncology · 2025Article
- Glioblastoma Neurovascular Progenitor Orchestrates Tumor Cell Type Diversity.bioRxiv : the preprint server for biology · 2024Article
- Glioblastoma Phagocytic Cell Death: Balancing the Opportunities for Therapeutic Manipulation.Cells · 2024Review
- Semi-automated approaches for interrogating spatial heterogeneity of tissue samples.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
Meningiomas are the most common primary intracranial tumors. Treatments for patients with meningiomas are limited to surgery and radiotherapy, and systemic therapies remain ineffective or experimental. Resistance to radiotherapy is common in high-grade meningiomas and the cell types and signaling mechanisms that drive meningioma tumorigenesis and resistance to radiotherapy are incompletely understood. Here, we report that NOTCH3 drives meningioma tumorigenesis and resistance to radiotherapy and find that perivascular NOTCH3+ stem cells are conserved across meningiomas from humans, dogs, and mice. Integrating single-cell transcriptomics with lineage tracing and imaging approaches in genetically engineered mouse models and xenografts, we show NOTCH3 drives tumor-initiating capacity, cell proliferation, angiogenesis, and resistance to radiotherapy to increase meningioma growth and reduce survival. To translate these findings to patients, we show that an antibody stabilizing the extracellular negative regulatory region of NOTCH3 blocks meningioma tumorigenesis and sensitizes meningiomas to radiotherapy, reducing tumor growth and improving survival. Significance: There are no effective systemic therapies to treat meningiomas, and meningioma stem cells are poorly understood. Here, we report perivascular NOTCH3+ stem cells to drive meningioma tumorigenesis and resistance to radiotherapy. Our results identify a conserved mechanism and a therapeutic vulnerability to treat meningiomas that are resistant to standard interventions.
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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.