Glioblastoma (GBM) is the most aggressive adult primary brain tumor and remains incurable. At present, there is still a large knowledge gap and lack of clinically relevant models to identify the molecular and cellular mechanisms that drive intrinsic and -de novo- treatment resistance in GBM. The aim of this project is to establish GBM organoid models expressing genetically encoded fluorescent tracers (confetti) that can be temporally ‘activated’ to enable lineage tracing and cell ablation and to visualize patters of clonal evolution in response to treatment or changes in the tumor microenvironment in a spatial and temporal manner within and between patients.
This project will enable, by developing a primary human tumor cell culturing platform, the understanding the impact of tumor cell mutations on stem cell renewal and differentiation and the identification of new interventions against recurrent treatment-resistant glioblastoma.