Three-Dimensional Cell Culture Systems in Pediatric and Adult Brain Tumor Precision Medicine

SIMPLE SUMMARY: High-grade brain tumors, including glioblastoma, are still incurable diseases. Extensive research has allowed new insights into tumor biology, for example, by exploring tumor–TME interactions or their mutational load. Recent advances in in vitro modeling of brain tumors have resulted in the establishment of three-dimensional brain tumor organoid models that recapitulate parenteral tumor characteristics in a more precise manner. This review summarizes the available organoid models in adult and pediatric brain tumors, their limitations, and their present applications. Furthermore, it focuses on their future potential for improving translational therapies based on a better understanding of the molecular bases of tumor biology. We provide researchers with an overview of the field, allowing them to choose a suitable model. ABSTRACT: Primary brain tumors often possess a high intra- and intertumoral heterogeneity, which fosters insufficient treatment response for high-grade neoplasms, leading to a dismal prognosis. Recent years have seen the emergence of patient-specific three-dimensional in vitro models, including organoids. They can mimic primary parenteral tumors more closely in their histological, transcriptional, and mutational characteristics, thus approximating their intratumoral heterogeneity better. These models have been established for entities including glioblastoma and medulloblastoma. They have proven themselves to be reliable platforms for studying tumor generation, tumor–TME interactions, and prediction of patient-specific responses to establish treatment regimens and new personalized therapeutics. In this review, we outline current 3D cell culture models for adult and pediatric brain tumors, explore their current limitations, and summarize their applications in precision oncology.