Glioblastoma Models for Preclinical Assays: A Strengths, Weaknesses and Purpose Overview

Glioblastoma (GB) is an extremely aggressive tumour for which effective therapy is still in its infancy. Although several candidate therapeutics have been identified in functional preclinical assays, clinical trials have not supported their effectiveness in GB patients. One reason for their poor clinical efficacy is that available preclinical models poorly mimic GB characteristics in patients. In this review article, we provide a comprehensive overview of GB preclinical models, which are classified according to their origin (animal or human), type and modelling strategy (2D or 3D cell culture, in vivo grafting or in silico modelling). Moreover, the article compares developing cut-ting-edge technologies, including GB derived organoids, bioprinting, mi-crofluidic devices, and their multimodal integration in tumor-on-chip sys-tems, which aim to replicate the tumour microenvironment with high pre-cision. In silico and in vivo approaches are also reviewed, including zebrafish transplantation models. The respective costs, benefits and purposes of each model system and/or modelling strategy are discussed in detail and com-pared. We highlight that the most appropriate, or combination of, GB pre-clinical models must be selected (or even customized) based on the specific aims and constraints of each study. Finally, to improve the reliability and translational relevance of GB research, we propose a practical roadmap that addresses critical challenges in preclinical assay development, ranging from short-term adjustments to long-term strategic planning.