PO44INVESTIGATION OF THE CLINICAL POTENTIAL OF AGENTS TARGETING EPIGENETIC MODIFICATIONS IN PAEDIATRIC EPENDYMOMA

Abstract

INTRODUCTION: Alterations in epigenetic modifications are known to play a key role in many types of cancer. Agents targeting these modifications are in clinical development, with the most advanced targeting histone de-acetylation (HDACi) and DNA methylation. Ependymoma is the second most common malignant paediatric tumour of the central nervous system. Currently there are few effective adjuvant therapies and prognosis remains poor. Recent studies suggest epigenetic alterations may be important in ependymoma development. The studies demonstrated that HDACi and de-methylating agents both inhibited ependymoma cell growth and therefore could be a potential therapeutic target. HDACi were also shown to induce neuronal differentiation suggesting epigenetic modifications may inhibit differentiation of ependymoma cells. METHOD: The affect the HDACi Vorinostat and the de-methylating agent Decitabine on ependymoma cell line growth were measured using an MTT assay. To analyse effects on induction of differentiation, expression of differentiation markers were measured following Vorinostat or Decitabine treatment of ependymoma cells. RESULTS: Vorinostat and Decitabine both inhibited the growth of ependymoma cell lines. Evidence of differentiation was seen after treatment with both agents. Expression of differentiation markers following Vorinostat or Decitabine treatment is undergoing analysis. CONCLUSION: Agents targeting histone de-acetylation and DNA methylation inhibit the growth of ependymoma cells, which may in part be due to an induction of differentiation. The data supports the potential of using these agents as novel therapies for ependymoma treatment.