ArticleCell death & disease2019
NPI-0052 and γ-radiation induce a synergistic apoptotic effect in medulloblastoma.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Organoids as next-generation models for investigating intracranial tumours.Molecular brain · 2026Review
- Marizomib in the therapy of brain tumors-how far did we go and where do we stand?Pharmacological reports : PR · 2025Review
- MiRNAs as major players in brain health and disease: current knowledge and future perspectives.Cell death discovery · 2025Review
- Personalising glioblastoma medicine: explant organoid applications, challenges and future perspectives.Acta neuropathologica communications · 2025Review
- The Proteasome Inhibitor CEP-18770 Induces Cell Death in Medulloblastoma.Pharmaceutics · 2024Article
- The pivotal role of irradiation-induced apoptosis in the pathogenesis and therapy of medulloblastoma.Cancer reports (Hoboken, N.J.) · 2024Review
- Organoids as a new approach for improving pediatric cancer research.Frontiers in oncology · 2024Review
- Applications of organoid technology to brain tumors.CNS neuroscience & therapeutics · 2023Review
- Modeling nervous system tumors with human stem cells and organoids.Cell regeneration (London, England) · 2023Review
- Three-Dimensional Cell Culture Systems in Pediatric and Adult Brain Tumor Precision Medicine.Cancers · 2022Review
- Dissecting super-enhancer driven transcriptional dependencies reveals novel therapeutic strategies and targets for group 3 subtype medulloblastoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Combination of BMI1 and MAPK/ERK inhibitors is effective in medulloblastoma.Neuro-oncology · 2022Article
- Role of MicroRNAs in the Development and Progression of the Four Medulloblastoma Subgroups.Cancers · 2021Review
- The multifaceted NF-kB: are there still prospects of its inhibition for clinical intervention in pediatric central nervous system tumors?Cellular and molecular life sciences : CMLS · 2021Review
- Cerebral organoids: emerging ex vivo humanoid models of glioblastoma.Acta neuropathologica communications · 2020Review
- Proteasome inhibition-a new target for brain tumours.Cell death discovery · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Medulloblastoma (MB) is the most common malignant solid paediatric brain tumour. The standard treatment for MB is surgical resection of the tumour, radiation and chemotherapy. This therapy is associated with high morbidity and adverse side effects. Hence, more targeted and less toxic therapies are vitally needed to improve the quality of life of survivors. NPI-0052 is a novel proteasome inhibitor that irreversibly binds the 20S proteasome subunit. This compound has anti-tumour activity in metastatic solid tumours, glioblastoma and multiple myeloma with a good safety profile. Importantly, NPI-0052 has a lipophilic structure and can penetrate the blood-brain barrier, making it a suitable treatment for brain tumours. In the present study, we performed an in silico gene expression analysis to evaluate the proteasome subunit expression in MB. To evaluate the anticancer activity of NPI-0052, we used a range of MB patient-derived MB cells and cell lines. The synergistic cell death of NPI-0052 with γ-radiation was evaluated in tumour organoids derived from patient-derived MB cells. We show that high expression of proteasome subunits is a poor prognostic factor for MB patients. Also, our preclinical work demonstrated that NPI-0052 can inhibit proteasome activity and activate apoptosis in MB cells. Moreover, we observe that NPI-0052 has a synergistic apoptotic effect with γ-radiation, a component of the current MB therapy. Here, we present compelling preclinical evidence that NPI-0052 can be used as an adjuvant treatment for p53-family-expressing MB tumours.
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