Deciphering cell communication networks to fight ETMR

Embryonal tumors with multilayered rosettes (ETMR)s are highly aggressive brain tumors that occur mainly in infants and very young children. Despite intensive chemotherapy, only 10-20% of children survive. Although a specific pattern of small RNA molecules, also called C19MC micro-RNA clusters, has been found to be a marker for ETMR, our understanding of the biology and treatment of this disease is still limited. Our study aims to improve the understanding and treatment of this disease using three main approaches. First, we aim to gain a deeper insight into the structure of these tumors. To do this, we will use a technique that provides information about the molecular properties and at the same time can visualize the spatial distribution of these. This technique is called "spatial transcriptomics". To achieve even higher resolution, these data are compared with RNA data of each cell previously obtained from the tumor material of the same patients. The high resolution allows us to identify rare cell populations, which could play a major role in therapy. Second, we will study the communication networks between the tumor and its immediate environment, focusing on interactions between receptors on the cell surface and ligands secreted by cells. Another communication tool of tumor cells are the 30-150nm extracellular vesicles (EVs) that are released by tumor cells into their environment, thereby affecting it. Finally, we will determine the potential of the discovered candidates for therapeutic intervention. For this purpose, the identified genes will be "switched off" in a cell culture experiment, which suppresses the transcription of the respective gene into a protein. We will then analyze whether this has an impact on tumor cell growth and survival. In addition, we will use computational models to analyze whether the selected drugs have the ability to cross the blood-brain barrier. Understanding the different cell populations within the tumor and cell-cell interactions is critical for effective cancer treatment. By taking a detailed and spatially resolved view of the tumor environment in ETMRs, we hope to gain important biological insights and identify potential therapeutic targets.