Glioblastoma metabolism and heterogeneity, in 3D organoids

Objectifs

Glioblastoma (GBM), a lethal brain tumor, represents one of the most common and aggressive primary brain tumors. By understanding the molecular basis for cancer cell metabolic dependencies and by identifying Achille’s heels for targeting these vulnerabilities, in a relevant physiological context, our research can provide a better understanding of tumor progression.

Therefore, our team focuses on the cellular and molecular mechanisms underlying cancer cell and cancer stem cell addiction to different metabolic pathways, and to design new strategies to exploit these vulnerabilities to halt GBM progression.

To do so, we developed innovative tools and cellular models (in 2D and in 3D) derived from GBM patients. Moreover, we have developed a tissue engineering in vitro approach to generate a pluripotent stem cell-derived human brain-like tissue and organoid in 3D. We demonstrated that GBM cells proliferate and develop into these brain-like tissues, generating a mixed tissue that mimics some critical and important features of the in vivo host/tumor interaction. This system represents a relevant and unique mini-brain model that can be used to study and understand molecular and cellular mechanisms underlying the interaction between the human neural tissue (made of functional neurons, astrocytes and oligodendrocytes) and GBM cells.

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