This project seeks to develop novel treatments for gliomas with mutations of isocitrate dehydrogenase. This mutation results in epigenetic alterations that cause suppression of genes that regulate cell growth at least partially due to the fact that the enzyme takes on new functional roles. Our goal is to further investigate how this suppression occurs and whether we can utilize therapies directed towards alleviating this suppression. We believe that the transcription factor, Olig2 is playing an important role in the growth and gene regulation of IDH mutant tumors.
We theorize that reducing the function of Olig2 through inhibition of its expression or its downstream effects, in combination with suppression of the mutant enzyme will enhance survival in patients with IDH mutant gliomas. During the first phase of this project, we will investigate our fundamental hypotheses and perform translational experiments to test the validity of our treatment strategies. The second phase of the project will utilize this information for clinical trials, in which we first use a short period of treatment to determine if our strategies cause the desired biochemical effects. If the desired results are achieved, we will undertake a longer, interventional trial.