Complementary role of mathematical modeling in preclinical glioblastoma: differentiating poor drug delivery from drug insensitivity

Glioblastoma is the most malignant primary brain tumor with significant heterogeneity and a limited number of effective therapeutic options. Many investigational targeted therapies have failed in clinical trials, but it remains unclear if this results from insensitivity to therapy or poor drug delivery across the blood-brain barrier. Using well-established EGFR-amplified patient-derived xenograft (PDX) cell lines, we investigated this question using an EGFR-directed therapy. With only bioluminescence imaging, we used a mathematical model to quantify the heterogeneous treatment response across the three PDX lines (GBM6, GBM12, GBM39). Our model estimated the primary cause of intracranial treatment response for each of the lines, and these findings were validated with parallel experimental efforts. This mathematical modeling approach can be used as a useful complementary tool that can be widely applied to many more PDX lines. This has the potential to further inform experimental efforts and reduce the cost and time necessary to make experimental conclusions. ### Competing Interest Statement The authors have declared no competing interest.