Research Progress of Brain Tumor Organoids
LI Linbo1,2, BIAN Shan2*
Primary brain tumors exhibit profound heterogeneity and a complex TME (tumor microenvironment) that traditional 2D cultures and PDX (patient-derived xenograft) models cannot fully recapitulate. BTOs (brain tumor organoids), generated via the self-organization of pluripotent stem cells or CSCs (cancer stem cells) into three-dimensional structures, preserve the genetic and phenotypic diversity of the original tumors while incorporating key elements of the human microenvironment. This review systematically summarizes three principal strategies for BTOs construction—patient somatic cell reprogramming, direct derivation from tumor specimens, and geneediting- driven approaches—and details their applications across major tumor subtypes, including glioblastoma, medulloblastoma, and diffuse intrinsic pontine glioma. In this review, recent advances in leveraging BTOs to dissect pathogenic mechanisms, study TME interactions, screen therapeutics, investigate drug resistance, and develop personalized precision therapies are highlighted. Additionally, critical challenges in model standardization, microenvironment complexity, and ethical-biosafety considerations are discussed. Emerging innovations—such as refined gene-editing protocols, multi-omics integration, microfluidic platforms, and AI-driven analyses—are also explored, with the goal of offering new insights and tools for brain tumor research and treatment.
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