Project information
Development of brain organoid models to study the role of cellular senescence in the pathogenesis of glioblastoma

Glioblastoma is a highly aggressive, untreatable brain tumor with a dismal prognosis and a negative socio-economic impact that significantly shortens life expectancy. There has been no improvement in glioblastoma therapy in the last decade. The part of this unfavorable situation is that current antiproliferative genotoxic therapies of malignant diseases, including radiotherapy and chemotherapy of glioblastoma, possess, besides overall toxicity, severe drawbacks going against intended therapeutic effects such as the induction of 1) epithelial-to-mesenchymal transition of surviving tumor cells leading to invasive migratory phenotype associated with suppression of cell division and therapy resistance; 2) mesenchymal-to-amoeboid transition resulting in even more invasive phenotype linked again to the therapy resistance; 3) cancer cell stemness associated with therapy resistance as well; and 4) cellular senescence in cancer (and stromal) cells leading to secretory phenotype triggering and supporting all the above traits together with immunosuppression. Therefore, to improve cancer medical treatment, there is a need to understand the exact mechanisms of these adverse biological effects to identify new therapeutic targets and to substitute antiproliferative genotoxic therapies with more efficient approaches lacking these adverse effects or to find adjuvant therapy to suppress them. The latter is the goal of this study focused specifically on GB – to find molecular pathways contributing to the harmful effects of currently used GB RCHT therapy, namely cell migration. There is little information about changes in brain tissue associated with the current therapy of GB.