Modeling of Malignant Glioma and Investigations into Novel Treatments

Abstract

With the advent of personalized medicine and large omics-based profiling studies into multiple diseases, new opportunities rise for the treatment of Malignant Glioma. This primary brain tumor remains unvariantly fatal and therefore urgently requires novel treatment options. In this thesis a novel model for glioma stem-like cells is characterized for molecular recapitulation of driving alterations found in patient tumors. In addition, the model is verified to reproduce in vitro the clinical outcome found in patients treated with the golden standard chemotherapeutic temozolomide.

As a result of these characterization studies the model was implemented in several drug screens to explore the possibility of augmentation through combination therapy with temozolomide and oncolytic virotherapy with Delta24-RGD, reovirus and herpes virus. Mechanistic studies into response profiles were undertaken, which provided leads for biomarkers for therapeutic effect and patient selection. In addition, several contemporary reviews are provided to further substantiate these findings and place the data into context with recently published work of others.

In conclusion, this thesis provides several leads into the implementation of patient tailored medicine for malignant glioma patients that should subsequently be further validated in animal and patient trials.