Transcription factor-based gene therapy to treat glioblastoma through direct neuronal conversion

Advances in organoid technology have transformed how gliomas are modeled and studied. Recent FDA and NIH initiatives further promote human-relevant organoid platforms for preclinical research. Glioma organoids can be broadly categorized into 3 main classes: Engineered organoids, which enable controlled modeling of gliomagenesis driven by specific mutations; patient-derived organoids, which preserve key molecular and histopathological features of the original tumors; and assembloids, which are designed to model tumor-microenvironment interactions. Together, these systems provide a human cell-relevant framework for investigating glioma biology, tumor-microenvironment crosstalk, and therapeutic responses and resistance. In this review, we provide a comprehensive overview of the spectrum of glioma organoid models, recognizing that different systems offer distinct and complementary strengths, and we offer practical guidance for selecting appropriate models and analytical readouts based on specific basic and translational research objectives. To address increasing methodological heterogeneity and fragmented terminology, we propose a foundational nomenclature framework for glioma organoid models to improve clarity and communication within the field. We highlight applications in technically challenging subtypes, including isocitrate dehydrogenase (IDH)-mutant gliomas and diffuse midline gliomas (DMGs). We also discuss key challenges—including scalability, standardization, microenvironment fidelity, and vascularization—and emerging innovations addressing these limitations. Finally, we call for greater collaboration and standardization within the glioma organoid community to accelerate the integration of organoid models into translational pipelines to redefine and refine preclinical modeling in neuro-oncology.