Ependymoma (EPN) is the third most common brain tumor in children. Surgery, followed by radiation therapy can be effective, but about 45 % of patients still remain incurable. No chemotherapy has shown efficacy for EPN thus far. Although nine molecular EPN subgroups with distinct clinical and demographic characteristic have been identified, an understanding of the molecular biology of EPN development and the identification of actionable targets to treat the disease are currently lacking. One of the main reason is that preclinical models such as cell lines, xenografts and animal models of the disease have not been widely available. However, substantial progress in establishing primary cell lines from ependymoma patients has recently been made by our collaborators. Several clinically relevant ependymoma cell lines (e.g. DKFZ-EP1NS) have been successfully established, which maintain primary tumor characteristic such as high tumorigenic potential and chemo-resistance. Interestingly, EPNs have a relatively stable genome. Accordingly, the importance of epigenetic alterations in EPN pathogenesis has become inevitably obvious. Therefore, epigenetic factors are promising targets for the development of novel treatment options. Hence, our project focuses on functional dissection of epigenetic regulators in EPN cells.
- Unravel specific targets for different ependymoma subgroups and transfer an already established shRNA screening protocol from a patient derived ependymoma line to other patient derived ependymoma cell lines.
- Investigation of primary candidate hits by independent approaches to delineate molecular mechanisms of EPN transformation and to identify treatment options.
- Comparison of drug resistance data with knockdown/knockout data to understand the molecular pathways that are affected in this tumor entity.
- Develop novel and innovative therapies in a patient-specific manner.