Personalized Therapy For High-risk Ependymoma Of Childhood
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About this
Project
Ependymoma is the third most common brain tumour of childhood, and current treatments are limited to surgery and radiation even in very young children. Both supratentorial and posterior fossa ependymoma are relatively chemotherapy resistant, and patients with relapsed or subtotally resected disease have very poor outcomes. As such, new treatment approaches are urgently required. Unfortunately, attempts to omit radiation from treatment have resulted in dismal survival, and as such, radiotherapy will likely need to remain a staple of therapy. In order to identify new targets for therapy, I have performed kinome screening and identified several signaling pathways which are specific to ependymoma (both RELA-fused and posterior fossa) including Ras/MAPK and JAK/STAT pathways, and these compounds are not active in either medulloblastoma stem cell models and normal fetal stem cell models. As such, I hypothesize that targeting upstream kinase inhibitors against Ras/MAPK is a rational treatment approach for childhood ependymoma.
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What are the goals of this project?
1) Chemical and genetic screening of therapeutic vulnerabilities in childhood ependymoma models
2) In vivo validation of compounds identified in Aim 1
What is the impact of this project?
Currently there are no therapies for ependymoma, either posterior fossa or supratentorial other than surgery and radiotherapy. Conventional chemotherapy has not been shown to be active in multiple studies. As such, the identification of new treatments is imperative for this high-risk brain tumour. Currently a limiting factor is the availability of model systems, particularly ones that propagate in vitro which can be used to identify new therapeutic vulnerabilities.
Why is the CBTN request important to this project?
We are requesting models of childhood ependymoma (both supratentorial and posterior fossa) which propagate in vitro, which are amenable to both chemical and genetic screening. As there is a paucity of ependymoma models that propagate in vitro, these will be extremely valuable to identify potential therapeutic targets which can be developed further.
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Ependymoma
Ependymoma
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 tumors