Advances in Glioblastoma Organoid Development and Applications in Personalised Therapy

Glioblastoma (GBM) remains one of the most lethal primary brain malignancies. Current treatment protocols have modestly improved the survival rate, while recurrence remains high. Conventional two-dimensional (2D) cell lines and animal xenografts have been essential for mechanistic discovery, yet they frequently fail to preserve patient-specific architecture, stem-like cell states, immune and stromal interactions, oxygen gradients, and clinically relevant drug responses. Organoid-based GBM models, including patient-derived glioblastoma organoids (GBOs) and related three-dimensional (3D) models, have therefore emerged as translational platforms that more closely approximate tumour biology while remaining experimentally tractable. This review summarises major trends in organoid-based GBM model development, from explant organoids to 3D bioprinted micro-physiological systems. It summarises how these models are being used to study GBM biology, the tumour microenvironment, therapeutic responses and their clinical translation. Furthermore, patient-derived GBM organoid models could become key tools for personalised medicine, as some can be generated within clinically meaningful time frames, preserve inter- and intra-tumoural heterogeneity, model treatment responses, and identify resistance pathways. However, organoid platforms are not yet standardised, and many still lack vascular perfusion, mature immune components, reproducible extracellular matrix composition, matched normal brain controls, and validated clinical endpoints. The next phase of research will require harmonised biobanking, integrated single-cell and spatial omics, automation, organoid-on-chip perfusion, vascular and immune engineering, ethical governance, and prospective clinical trials that test whether organoid-guided treatment improves outcomes. Overall, organoid-based GBM models should be viewed not as replacements for all preclinical models but as patient-focused human experimental systems that can bridge molecular profiling, functional drug testing, and precision neuro-oncology.