Determining Efficacy of Epigenetic Intervention-based Treatments for Targeting EWS-FLI1 Activity in Ewing Sarcoma
Developing effective Ewing sarcoma treatments is an imperative field of research due to its alarmingly high relapse rate with poor prognosis. This rare, aggressive type of cancer forms in the bones and soft tissues due to the EWS-FLI1 fusion gene, an oncodriver. Current treatments for Ewing sarcoma focus on tumor removal and targeting certain proteins that help the tumor grow, such as angiogenic factors. A promising new approach is aimed at epigenetically treating the cancer. It has been proposed that EWS-FLI1 recruits histone acetyltransferases and transcription coactivators for oncogenic activity which have profound abilities to induce epigenetic changes. This research project explored how targeting EWS-FLI1 activity with epigenetic methods affected Ewing sarcoma cell lines. The efficacy of the compounds was deduced by monitoring target gene transcription through western blot analysis of active chromatin markers, acetylated H3K18 and H3K27. The results indicate that one compound was able to completely reduce H3K18 and H3K27 acetylation in both Ewing sarcoma cell lines after a 12-hour incubation. Additionally, other tested compounds were able to decrease H3K18 and H3K27 acetylation compared to the control in both cell lines. The decrease in histone H3 acetylation correlates to a decrease in EWS-FLI1 activity which impedes further malignant cell transformations. This research provides evidence for efficacy and demonstrates the potential of epigenetic intervention-based treatments for Ewing sarcoma.