Emerging Brain Tumor Organoid Models for Studying Tumor Heterogeneity, Microenvironmental Interactions, and Therapeutic Response.

Authors

Fermisk Saleh, Carol Schuurmans

Published in

Journal of neurochemistry. Volume 170. Issue 11.

Abstract

Brain tumors are genetically and cellularly heterogeneous and interact extensively with neural, vascular, immune, and extracellular microenvironments that conventional experimental models reproduce incompletely. This review examines how brain tumor organoids are generated, how they have been applied in brain tumor research, and the challenges that must be overcome for broader application. Current approaches differ along two largely independent axes: whether tumor cells are derived directly from patient tissue or generated through defined genetic alterations, and whether the surrounding microenvironment is retained from the source tissue or deliberately reconstructed. We discuss how these models have been used to study genetic drivers of tumor initiation, intratumoral heterogeneity, tumor-microenvironment interactions, mechanisms of invasion, and patient-specific therapeutic responses and resistance. Across these applications, organoids have provided experimentally tractable systems in which to investigate tumor cell-state plasticity, tumor-neural interactions, microenvironmental regulation of tumor behavior, and variability in treatment response while preserving features of human disease often lost in conventional systems. At the same time, model establishment remains variable, cultures can diverge during prolonged propagation, and vascular and immune compartments remain incompletely represented. Brain tumor organoids therefore complement rather than replace two-dimensional culture systems, genetically engineered mouse models, and patient-derived xenografts. Future progress will depend on rigorous standardization of organoid generation and characterization, together with the selective incorporation of biological and engineering complexity according to the specific experimental or therapeutic question being addressed.

PMID:
43031347
Bibliographic data and abstract were imported from PubMed on 14 Nov 2026.

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