Reaggregated Glioblastoma Organoids Compare Radiation Responses Across 48 Patients
A reaggregated organoid collection linked radiation responses with survival in corresponding patients. Expression-based analyses then identified BET inhibitors for testing as radiosensitizers.
A Quantitative Radiation-Response Collection
A University of Pennsylvania-led team developed reaggregated glioblastoma organoids to compare radiation responses across models from 48 patients. The platform was designed to standardize quantitative radiation-response testing across patient-derived models.
Radiation responses in the organoids correlated with the survival duration of the corresponding patients who received standard-of-care radiotherapy. Transcriptomic analyses identified expression signatures associated with relatively sensitive and resistant organoid responses, adding molecular information to the functional comparison.
From Expression Signatures to a Combination Test
The researchers used connectivity mapping against perturbational datasets to identify compounds that might suppress the resistant signature or enhance the sensitive one. Subsequent experiments found that inhibitors of bromodomain and extraterminal (BET) proteins enhanced radiotherapy activity in organoid and xenograft models. The treatment also reduced the radioresistance-associated expression signature.
The study therefore links several stages of a preclinical investigation: measuring radiation response in patient-derived tissue models, identifying associated molecular features and testing a candidate combination. The patient-survival relationship and the organoid combination experiments address different parts of that sequence. The reported clinical association provides context for further validation of the radiation assay.