Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma
— Categories: Ependymoma Research Articles Posted on July 24, 2020
Ependymomas are glial tumors that occur throughout the central nervous system. Of the nine distinct molecular types of ependymoma, posterior fossa A (PFA) ependymomas, found in the hindbrain of infants and young children, are the most prevalent type. In this publication, the investigators have identified a metabolic-epigenomic link in PFA ependymomas that informs the phenotype of PFA ependymoma and possible development of novel therapeutic strategies for these lethal cancers.
Dr. Antony MichealRaj, an Oncology Research Fellow from The Hospital for Sick Children in Toronto, Canada shares a summary of their findings.
“Our previous research findings showed that the PFA brain tumours emerge very early in a child’s development and, remarkably, there are no specific genetic mutations that are known to cause these tumours. Instead, these tumours possess a unique way of regulating what genes are on or off – a unique epigenetic landscape. We observed that PFA ependymoma tumours have an enriched hypoxia (response to low oxygen level) signature which is correlated with poor survival.
These unusual scenarios pushed us to investigate how hypoxia linked with ependymoma and its epigenetics. First, we showed hypoxia (low oxygen) environment is not only important for the establishing disease models, also quite essential for PFA ependymomas survival. We further explored the underlying mechanism where hypoxia regulate genes expression and availability “key metabolites” that collectively contributes to epigenetic profiling of ependymoma. We have identified a highly linked metabolic-epigenomic phenotype in PFA ependymomas that informs both the phenotype of PFA ependymoma, and opportunities for development of novel therapeutic strategies.
Additionally, we can screen FDA-approved drugs on PFA disease models we have developed, which will enable us find potential chemotherapies rapidly. Since there are currently no approved medicines that work for this type of cancer, if we find a drug that works, it could potentially become the standard of care for ependymomas.”