A standardized patient-derived glioblastoma organoid platform for evaluating radiotherapy efficacy and overcoming resistance
Year: 2026
Type: article
Abstract: Patient-derived glioblastoma (GBM) organoids (GBOs) maintain characteristics of their original tumors; however, they have not been widely applied to systematically assess therapy responses at scale or elucidate mechanisms underlying treatment resistance. Here, we develop a standardized reaggregated GBO (rGBO) platform for scalable, quantitative evaluation of radiation responses across 48 patients with GBM. Radiation responses in rGBOs correlate with the survival duration of corresponding patients treated with standard-of-care radiotherapy. Transcriptomic analyses identify gene signatures associated with radiosensitivity and radioresistance. Connectivity mapping with perturbational datasets identifies a panel of compounds with potential for reducing radioresistant and enhancing radiosensitive signatures. Subsequent testing demonstrates that inhibitors of bromodomain and extraterminal (BET) family proteins enhance radiotherapy efficacy in GBO and xenograft models by downregulating the radioresistant signature. Together, our study highlights the potential of rGBOs for standardizing therapeutic screening, evaluating patient-specific responses, identifying associated molecular features, and developing strategies to overcome treatment resistance.
Source: Cell Reports Medicine
Authors: Xin Wang, Yusha Sun, Prithvi Sinha, Ruiying Su, Daniel Y. Zhang, Kristen H. Park, Yao Fu, Weifan Dong, Zhijian Zhang, Qing Wang, Daniel H. Geschwind, Riki Kawaguchi, Emily Ling-Lin Pai, Maria A. Gubbiotti, Robert Colbourn, Nduka M. Amankulor, Jay F. Dorsey, MacLean P. Nasrallah, Stephen J. Bagley, Zev A. Binder, Donald M. O’Rourke, Yi Fan, Guo-li Ming, Hongjun Song
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Award: G796868690
OpenAlex ID: W7220845520