Date of Completion

Spring 5-1-2019

Project Advisor(s)

Joseph LoTurco

University Scholar Major

Physiology and Neurobiology

Disciplines

Cancer Biology | Chemical and Pharmacologic Phenomena | Developmental Biology | Developmental Neuroscience | Genetic Phenomena | Medical Neurobiology | Molecular and Cellular Neuroscience | Molecular Genetics | Neoplasms | Neurosciences

Abstract

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of all ependymomas. With a high mortality rate in ependymoma patients and the current lack in effective treatment methods for such brain tumors, advancement in treatment targets and mechanisms is necessary to improve patient survival. In this study, we assess the use of Notch inhibitors and JQ1 for their effectiveness in inhibiting the growth of C11orf95-RELA transformed cells isolated from primary brain tumors in mice. We find that both the BET bromodomain inhibitor JQ-1 and the FGFR inhibitor AZD4547 inhibit growth of C11orf95-RELA transformed cells and that the BET domain inhibitor JQ1 does so with the highest potency.

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