Project information
Unraveling Molecular Mechanisms of Glioblastoma Treatment Resistance and Recurrence: Insights from a 3D GLICO Model

Project Identification
Project Period
5/2024 - 12/2027
Investor / Pogramme / Project type
Ministry of Health of the CR
MU Faculty or unit
Faculty of Medicine
Cooperating Organization
St. Anne's University Hospital Brno

Glioblastoma IDH-wildtype WHO G4 (GB) is a primary malignant brain tumor characterized by its resistance to therapy and poor prognosis. Despite advances in surgical techniques, targeted radiotherapy, and chemotherapeutics, GB remains incurable with limited survival rates and underlying mechanisms of recurrence poorly understood. This project aims to use state-of-the-art biomedical technology to study residual GB cells clustered specifically at the resection border, likely promoting treatment resistance and invasive behavior. By analyzing tissue samples from the tumor periphery and employing advanced in vitro models such as stem cells-derived cerebral organoids, we will aim to elucidate the molecular signature of these cells and their role in tumor recurrence. We will also evaluate the expression signature changes in cerebral organoids upon GB infiltration, shedding new light on the microenvironmental changes in the brain imposed by tumor growth. Lastly, we will also perform a proof-of-concept study where patients-derived tumoroids will be used for in vitro drug testing. The project will combine advanced cell culture techniques with modern analytical methods, such as single-cell mRNA sequencing and tissue clearing, followed by functional experiments to confirm results. The ultimate goal is to uncover the molecular mechanisms driving glioblastoma recurrence and identify molecular targets for potential future therapy.

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