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A standardized patient-derived glioblastoma organoid platform for evaluating radiotherapy efficacy and overcoming resistance

ABSTRACT: Patient-derived glioblastoma organoids (GBOs) maintain characteristics of original tumors, though they have not been applied to assess therapeutics and investigate treatment resistance. In this study, we developed a standardized reaggregated GBO (rGBO) platform for scalable therapy screening and evaluated the efficacy of radiotherapy using rGBOs across 48 patients. Radiation responses in rGBOs correlated with clinical outcomes of their corresponding patients treated with standard-of-care radiotherapy. Transcriptomic analyses identified gene signatures differentiating responsive rGBOs from resistant ones. Connectivity mapping with perturbational datasets nominated a panel of drugs capable of decreasing radioresistant and elevating radiosensitive signatures, and subsequent testing demonstrated that bromodomain and extraterminal (BET) family protein inhibitors enhances radiotherapy efficacy in GBO and xenograft models by downregulating radioresistant and inflammatory signatures. Together, our study highlights the potential of rGBOs for standardizing therapy screening, assessing patient-specific treatment responses and associated molecular features, as well as developing novel combination therapies to overcome treatment resistance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE300985 | GEO | 2026/08/20

REPOSITORIES: GEO

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