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This thesis explores new ways to better understand and treat brain tumors in children. The focus was on two rare types of tumors: ependymomas and embryonal tumors with multilayered rosettes (ETMR). Because these tumors are difficult to treat and occur in only a small number of patients, we developed models that closely mimic them in order to do more research. To do this, we used techniques such as mini-brains (organoids), lab-grown tumor samples (tumoroids), and mouse models.

An important part of the research focused on so-called fusion proteins, where two genes merge into one. These fusions play a major role in the development of certain childhood brain tumors. In this thesis, we studied them in more detail to capture the complete playing field of fusions that create pediatric brain tumors. By introducing these fusion proteins into our mini-brains, we were able to recreate ependymomas in the lab. This allowed us to observe how these tumors develop and how they interact with their surroundings. We also found that some types of these tumors respond better to certain drugs than others.

For ETMR, a very rare brain tumor, we also developed models. These showed that ETMR tumors often don’t respond well to standard treatments. However, testing multiple drugs in these models did suggest that some experimental drugs could be promising.

The results of this thesis show that these new models are valuable tools to better understand childhood brain tumors and to search for more effective treatments. This offers hope for improved outcomes for young patients with these diseases.