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| Home > Publications database > Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy. |
| Home > Publications database > Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy. |
| Journal Article | DKFZ-2025-00346 |
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2025
Elsevier
Amsterdam [u.a.]
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Please use a persistent id in citations: doi:10.1016/j.stem.2025.01.002
Abstract: Tumor organoids are important tools for cancer research, but current models have drawbacks that limit their applications for predicting response to therapy. Here, we developed a fast, efficient, and complex culture system (IPTO, individualized patient tumor organoid) that accurately recapitulates the cellular and molecular pathology of human brain tumors. Patient-derived tumor explants were cultured in induced pluripotent stem cell (iPSC)-derived cerebral organoids, thus enabling culture of a wide range of human tumors in the central nervous system (CNS), including adult, pediatric, and metastatic brain cancers. Histopathological, genomic, epigenomic, and single-cell RNA sequencing (scRNA-seq) analyses demonstrated that the IPTO model recapitulates cellular heterogeneity and molecular features of original tumors. Crucially, we showed that the IPTO model predicts patient-specific drug responses, including resistance mechanisms, in a prospective patient cohort. Collectively, the IPTO model represents a major breakthrough in preclinical modeling of human cancers, which provides a path toward personalized cancer therapy.
Keyword(s): brain metastasis ; glioblastoma ; patient tumor organoid ; predictive patient model ; temozolomide ; tumor heterogeneity
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