ArticleRadiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology2021
Effects of the DRD2/3 antagonist ONC201 and radiation in glioblastoma.
Article in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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
19 citing papers in PubMed, 22 citations in OpenAlex.
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- ONC201 enhances the radiosensitivity of small-cell lung cancer via inhibition of the FAK signaling pathway.iScience · 2026Article
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Long-term survival in glioblastoma patients treated with dopamine agonists: A report of two cases and implications for drug repurposing.Surgical neurology international · 2026Article
- Integrative Transcriptomic and Perturbagen Analyses Reveal Sex-Specific Molecular Signatures Across Glioma Subtypes.Cancers · 2025Article
- Investigating the Effects of ONC206 Alone and in Combination with Cisplatin on Ovarian Cancer Cell Models.Current issues in molecular biology · 2025Article
- Combined quetiapine and radiation therapy approach to treat mesothelioma-initiating cells and increase survival in a mouse model of mesothelioma.bioRxiv : the preprint server for biology · 2025Article
- Synergistic combination of perphenazine and temozolomide suppresses patient-derived glioblastoma tumorspheres.Neuro-oncology · 2025Article
- Radiation-induced cellular plasticity primes glioblastoma for forskolin-mediated differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Effects of dopamine receptor antagonists and radiation on mouse neural stem/progenitor cells.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2024Article
- Combining the constitutive TRAIL-secreting induced neural stem cell therapy with the novel anti-cancer drug TR-107 in glioblastoma.Molecular therapy. Oncology · 2024Article
- The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models.Neuro-oncology · 2024Article
- Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1.Cancer research communications · 2024Article
- Radiation-Induced Cellular Plasticity: A Strategy for Combatting Glioblastoma.bioRxiv : the preprint server for biology · 2024Article
- Metabolic vulnerability of cancer stem cells and their niche.Frontiers in pharmacology · 2024Review
- Neurotransmitters: Potential Targets in Glioblastoma.Cancers · 2022Review
- Review: Neurological Complications From Therapies for Pediatric Brain Tumors.Frontiers in oncology · 2022Review
- MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma.International journal of molecular sciences · 2021Article
- Nuclear and membrane-bound hormone receptors in glioblastoma: Expression, functionality, and therapeutic implications.Neuro-oncology advancesReview
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundGlioblastoma (GBM) is the deadliest of all brain cancers in adults. The current standard-of-care is surgery followed by radiotherapy and temozolomide, leading to a median survival time of only 15 months. GBM are organized hierarchically with a small number of glioma-initiating cells (GICs), responsible for therapy resistance and tumor recurrence, suggesting that targeting GICs could improve treatment response. ONC201 is a first-in-class anti-tumor agent with clinical efficacy in some forms of high-grade gliomas. Here we test its efficacy against GBM in combination with radiation.
methodsUsing patient-derived GBM lines and mouse models of GBM we test the effects of radiation and ONC201 on GBM self-renewalin vitro and survivalin vivo.A possible resistance mechanism is investigated using RNA-Sequencing.
resultsTreatment of GBM cells with ONC201 reduced self-renewal, clonogenicity and cell viabilityin vitro. ONC201 exhibited anti-tumor effects on radioresistant GBM cells indicated by reduced self-renewal in secondary and tertiary glioma spheres. Combined treatment of ONC201 and radiation prolonged survival in syngeneic and patient-derived orthotopic xenograft mouse models of GBM. Subsequent transcriptome analyses after combined treatment revealed shifts in gene expression signatures related to quiescent GBM populations, GBM plasticity, and GBM stem cells.
conclusionsOur findings suggest that combined treatment with the DRD2/3 antagonist ONC201 and radiation improves the efficacy of radiation against GBMin vitroandin vivothrough suppression of GICs without increasing toxicity in mouse models of GBM. A clinical assessment of this novel combination therapy against GBM is further warranted.
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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.