Pediatric ependymoma is a brain cancer that results in significant morbidity and mortality for children, especially for patients whose tumors relapse and spread after initial treatment. A better understanding of the molecular pathways that drive tumorigenesis and metastasis in these tumors is a critical step in the development of new therapies. A team led by Pablo Gonzalez-Camara of the University of Pennsylvania is working to uncover the network of signals that regulate the formation and progression of ependymoma. Ependymal tumors are classified into nine molecular groups, each associated with a distinct anatomical location, age of onset, and prognosis. The team is focused primarily on posterior fossa group A (PFA), the most common type of ependymoma in children, representing about 70% of cases.
By developing and using novel topology-based computational methods to analyze molecular profiling data from individual cells harvested from primary and metastatic PFA tumors, the team will build regulatory network models of the dynamic cellular processes that drive tumor growth. Preliminary data have revealed the importance of Wnt/R-spondin, IL1β, and TGF-β signaling in stem cell proliferation and migration in ependymoma. The signaling network models generated by this project will generate hypotheses for the selection and combination of existing approved or experimental therapeutic agents for testing in ependymoma. The researchers also expect that this work will lead to new computational tools that can be broadly applied to the study of regulatory mechanisms in all types of cancer.
Aubin RG, Troisi EC, Montelongo J, Alghalith AN, Nasrallah MP, Santi M, Camara PG. Pro-inflammatory cytokines mediate the epithelial-to-mesenchymal-like transition of pediatric posterior fossa ependymoma. Nat Commun. 2022.