Ependymoma is a heterogeneous disease comprising at least nine distinct molecular groups. The most frequent and most aggressive groups of ependymoma are the RELA and PFA groups that predominantly occur in children. Although in recent years we and others identified the main drivers of these groups, the options how to target them therapeutically are still very limited. Therefore more insight in what is driving these tumors and how they can be targeted is needed. Recent studies performed in our lab in Heidelberg in collaboration with others around the world using either single cell RNA sequencing (Gojo et al., 2020) or Hi-C to map the 3D genome of ependymomas (Okonechnikov et al., ms in preparation) have identified several new therapeutic vulnerabilities. Some of them have been validated already in the few ependymoma cell lines that are around using drugs targeting the essential proteins, but further validations are needed in additional in vitro models representing the (heterogeneity) of the disease. For this we want to make use of the newly established CBTN ependymoma cell lines. The most promising drugs or drug combinations will subsequently also be tested in in vivo PDX models of ependymoma.
What are the goals of this project?
The goal of this project is to validate the importance of ependymoma group specific genes identified in previous studies in ependymoma cell lines using either shRNA /CRISPRcas9 constructs to inhibit/knockout the expression of these genes or specific targeted drugs when available
What is the impact of this project?
New therapeutic strategies are urgently needed for RELA and PFA ependymoma. Results of our study using the CBTN cell lines and PDX models may lead to new treatment options for ependymoma patients.
Why the CBTN request is important to this project?
The availability of ependymoma cell lines and PDX models representing the disease is limited and therefore the source of these 7 requested ependymoma cell lines and the PDX model is of high value for our project to test new therapeutic vulnerabilities.
The Children's Brain Tumor Network will contribute to this project by providing cell lines and PDX models.
Ependymomas arise from ependymal cells that line the ventricles and passageways in the brain and the center of the spinal cord. Ependymal cells produce cerebrospinal fluid (CSF). These tumors are classified as supratentorial or infratentorial. In children, most ependymomas are infratentorial tumo