Abstract
Glioblastoma is an aggressive and prevalent form of brain cancer characterized by rapid tumor cell migration and invasion into surrounding healthy tissues, making it resistant to conventional treatments. Despite advances in therapeutic approaches, patient prognosis remains poor, with a median survival of approximately 15 months. Tumor cell infiltration along perivascular spaces and white matter tracts is a major driver of recurrence, underscoring the need for experimental models that accurately capture these invasive behaviors. Animal models remain indispensable for this purpose, offering insights that cannot be fully replicated in vitro. This review focuses on applying animal models to elucidate the mechanisms underlying glioblastoma cell migration and invasion, which remain critical to improving therapeutic outcomes. By comparing the advantages of animal models with in vitro systems, we highlight the unique insights animal models provide, particularly in capturing the intricate dynamics of tumor cell motility. In particular, patient-derived xenograft (PDX) models preserve patient-specific heterogeneity and invasion patterns, such as white matter tract and perivascular infiltration, enabling clinically relevant drug testing. Zebrafish xenografts provide real-time, high-resolution visualization of tumor-vascular interactions, facilitating rapid assessment of invasion dynamics and early-stage drug screening. Genetically engineered models (GEM) allow precise discrimination of how defined genetic alterations drive specific invasive routes in the brain. Furthermore, we explore the use of advanced imaging techniques in these models to monitor tumor progression in real time. Moreover, we discuss the major drawbacks of these animal models, such as incomplete immune components and tumor microenvironment recapitulation. Ultimately, animal models are essential for bridging the gap between basic research and clinical application, offering a powerful platform for developing targeted strategies to combat glioblastoma's relentless progression.