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Automated and personalized glioblastoma tumor organoid drug screening platform exposes sensitivity to proteasome and HDAC inhibitors

Personalized drug screening aims to improve the survival of glioblastoma (GBM) patients by identifying effective patient-individual drugs. Therefore, we conducted an automated high-throughput drug screening (aHTS) on standardized patient-derived glioblastoma tumor organoids (TOs). Robot-assisted aHT...

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Autori principali: Jungwirth, Gerhard (Autore) , Paul, Adrian (Autore) , Wöllner, Amélie (Autore) , Warta, Rolf (Autore) , Cao, Junguo (Autore) , Fermi, Valentina (Autore) , Jassowicz, Lena (Autore) , Dao Trong, Huy Philip (Autore) , Deimling, Andreas von (Autore) , Debus, Jürgen (Autore) , Krieg, Sandro (Autore) , Unterberg, Andreas (Autore) , Abdollahi, Amir (Autore) , Herold-Mende, Christel (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 16 June 2026
In: npj precision oncology
Year: 2026, Volume: 10, Pages: 1-10
ISSN:2397-768X
DOI:10.1038/s41698-026-01552-5
Accesso online:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41698-026-01552-5
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41698-026-01552-5
Testo
Note sull'autore:Gerhard Jungwirth, Adrian Paul, Amélie Wöllner, Rolf Warta, Junguo Cao, Valentina Fermi, Lena Jassowicz, Philip Dao Trong, Andreas von Deimling, Juergen Debus, Sandro Krieg, Andreas Unterberg, Amir Abdollahi & Christel Herold-Mende
Descrizione
Riassunto:Personalized drug screening aims to improve the survival of glioblastoma (GBM) patients by identifying effective patient-individual drugs. Therefore, we conducted an automated high-throughput drug screening (aHTS) on standardized patient-derived glioblastoma tumor organoids (TOs). Robot-assisted aHTS was performed on TOs from 11 GBM patients. TOs fully compacted after two days, and the size remained stable over 10 days. TOs proliferated over time, and immunofluorescence stainings (GFAP, Tenascin C) confirmed tissue-like architecture. Anti-glioma effects with the lowest drug concentrations were achieved for proteasome inhibitors (carfilzomib, bortezomib, ixazomib), and HDAC inhibitors (panobinostat, romidepsin). Plasma Cmax-based drug levels (Cmax/IC50 > 1) used as a surrogate were only achieved for the three proteasome inhibitors and the HDACi romidepsin. The impact of their drug targets PSMB5 and HDAC1/2 on the growth of GBM cells was successfully validated by RNAi experiments. We established an aHTS platform for GBM TOs, and identified proteasome and HDAC inhibitors as promising drugs for the treatment of GBMs.
Descrizione del documento:Veröffentlicht: 16. Juni 2026
Gesehen am 25.09.2026
Descrizione fisica:Online Resource
ISSN:2397-768X
DOI:10.1038/s41698-026-01552-5

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