Abstract BACKGROUND Glioblastoma is the most common and aggressive primary brain tumor in adults. Despite recent progress, prognosis remains poor. This study presents a patient and tumor-specific drug screening approach using a novel platform for continuous imaging of patient-derived mini-tumors to identify effective therapies for newly diagnosed and recurrent glioblastoma. MATERIAL AND METHODS Patient-derived glioblastoma cells were co-cultured with primary astrocytes in a 384-well format to generate three-dimensional microtumors. A panel of 30 clinically relevant drugs, selected for their blood-brain barrier permeability and clinical data (off-label use), were tested at peak plasma concentrations. Drug responses were evaluated using an automated live time imaging platform, with efficacy determined through treatment-to-control ratios (TC-values) and mini-tumor response data. RESULTS Drug response analysis revealed substantial inter-individual variability. While some patient-derived cells responded to multiple compounds, others showed limited sensitivity. In all tested cells, at least one treatment was identified with higher efficacy than standard-of-care agents temozolomide and lomustine. Notably, a BRAF/MEK inhibitor combination (tovorafenib/pimasertib) consistently demonstrated strong activity across several microtumors, suggesting potential broad applicability. CONCLUSION This study demonstrates the feasibility and indicates the potential of dynamic drug sensitivity testing platforms to identify personalized treatment strategies for glioblastoma. Further evaluation in clinical trials is required to validate these findings.
Bouzereau et al. (Wed,) studied this question.