Quantifying glioblastoma drug penetrance from experimental data

Abstract

Poor clinical trial outcomes for glioblastoma (GBM) can be attributed to multiple possible causes. GBM is heterogeneous, such that there is a chance of treatment-resistant cells coming to predominate the tumor, and due to the blood brain barrier (BBB) it is also possible that therapy was inadequately delivered to the tumor. Mathematically modeling the dynamics of therapeutic response in patient-derived xenografts (PDX) and fitting the mathematical model to bioluminescence imaging flux data, we may be able to assess the degree to which both drug resistance and drug penetrance are driving varied responses to these therapies.