Abstract

To date, molecular targeted agents have failed to improve outcomes for glioblastoma patients, despite promising pre-clinical data. The discrepancy between pre-clinical and clinical effects may be at least partly explained by the widespread use of conventional 2-dimensional cell culture and xenograft models derived from established cell lines, which fail to recapitulate key features of the human disease. We have developed a novel 3-dimensional cell culture system in which effects of radiotherapy-drug combinations differ from 2D systems and replicate outcomes of clinical trials. The model will be described along with illustrative data.For in vivo testing of promising combinations, intracranial injection of primary GBM cells that have been cultured to enrich the stem-like population generates orthotopic xenografts that recapitulate key histopathological features of GBM and can be used for pharmacokinetic, pharmacodynamic and efficacy studies of promising therapeutic combinations. These models are suitable for functional imaging studies and image guided irradiation protocols.