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