Glioblastoma: Validation and Comparison Between Primary Tumor and Its Murine Model

Plain-language summary

Despite maximal safe surgery followed by combined chemo-radiation therapy, the outcome of patients suffering from glioblastoma (GBM) remains extremely poor with a median survival of 15 months. Hence, new avenues have to be taken to improve outcome in this devastating disease. Given their intracerebral localization and their highly invasive features, GBM pose some specific challenges for the development of adequate tumor models. Orthotopic xenograft models directly derived from the tumor of a patient might represent an attractive perspective to develop patient-specific targeted therapies. This approach remains however to be validated for GBM as it offers specific challenges, including the demonstration that the properties of xenograft models validly represent treatment relevant features of the respective human tumors. In this innovative project the investigators aim to compare and validate an approach of paired human GBM and respective derived orthotopic xenografts in the mouse brain on the levels of radiological behavior and metabolism of the tumors, as determined by high resolution MRI of the patients (7T MRI) and the respective orthotopic mouse xenografts (14.1T MRI), as well as on the level of the transcriptome, genome, and methylome of the original GBM tissue and respective derived xenografts/glioma sphere lines. The data will be integrated in multidimensional analyses and interrogated for similarities and associations with molecular GBM subtype. This pilot project will provide the basis for the crucial next steps, which will include drug intervention studies. New promising drugs, tested pre-clinically in the mouse orthotopic xenograft models established here using the radiologic/metabolic/molecular procedures described for this project, will be taken into patients in phase 0 studies. GBM patients will receive radiologic/metabolic follow-up using high resolution MRI under drug treatment, followed by resection of the tumor and subsequent acquisition of molecular data.

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