GBM model throughput, complexity, and cancer hallmarks. The figure illustrates the incorporation of clinically relevant hallmarks of gliomas and the trade-offs between throughput and complexity across various GBM models: in vitro (2D cell lines, 3D GSCs, TOs), ex vivo (tumor explants, co-cultures like GLICOs and GBM-on-a-chip), and in vivo (syngeneic and PDX mouse models). These models range from cell lines that capture cell-autonomous cancer hallmarks to PDXs and GLICOs that incorporate tumor-specific factors like the BBB and immune components. The most complex future models should account for patient-specific factors, including clinical and treatment history. Created in BioRender.