Translational Insights and Clinical Relevance of Glioblastoma 3D In Vitro Models.

Abstract

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, highlighting the urgent need for experimental models that can faithfully recapitulate its complex biology. In vitro models are essential tools for investigating GBM biology and for preclinical drug development. Conventional two-dimensional cultures fail to reproduce the three-dimensional organization, cellular heterogeneity, and micro-environmental interactions that influence tumor growth and therapeutic response. In vitro GBM models serve as the first step in the translational pipeline, enabling drug screening, mechanistic studies, biomarker discovery, and personalized medicine approaches. Despite their limitations, including a lack of full microenvironmental context and blood-brain barrier (BBB) considerations, these models provide critical insights that inform preclinical animal studies and early-phase clinical trials. This review critically describes the variety of three-dimensional (3D) in vitro models that have been developed, including spheroids, organoids, organ-on-chip systems and describes advantages and drawbacks of these platforms for investigating tumor progression, cell communication, and responses to therapies. Indeed, understanding the strengths and limitations of GBM in vitro models is essential for designing translational studies that can bridge laboratory research with clinical applications. Future advances, including the use of sophisticated bioprinting approaches to generate spatially organized, multilayered microenvironments incorporating diverse cell populations in complex co-culture systems, are anticipated to markedly improve predictive power and therapeutic outcomes in individualized patient care .