Malignant glioma is the most common primary brain tumor with approximately 20,000 new cases expected in the United states in 2018. It has been shown that approximately 12% of glioblastoma multiforme (GBM) and ⅓ of all adult gliomas display mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes. To date, no effective therapeutics exist that show specificity towards IDHMUT gliomas. In order to find a potential therapeutic for IDHMUT gliomas, the Persson lab conducted a high throughput drug screen of over 2,177 FDA-approved compounds. Beta-lapachone emerged as a potential therapeutic to specifically target IDHMUT cancer cells with little to no cytotoxicity in human fetal neural stem cells (hfNSCs). High NAD(P)H:quinone oxidoreductase 1 (NQO1) expression has been used previously as an indicator for B-lap cytotoxicity in IDHWT cancers. NQO1 converts Beta-lapachone into a hydroquinone, driving ROS levels and NAD+ depletion to result in cell death. Our data suggests that IDHMUT cancer cell lines have a higher NQO1:catalase ratio and are more sensitive to Beta-lapachone treatment than IDHWT lines with similar NQO1 expression. We have also shown that Beta-lapachone is capable of crossing the blood-brain barrier, driving reactive oxygen species and DNA oxidation only 48 hours after initial treatment. We plan to use human iPSCs with induced IDHMUT as an isogenic system to further understand the link between IDH status and response to Beta-lapachone. We will also carry out in vivo experiments with ARQ761, a Beta-lapachone prodrug, on mice with patient-derived xenografts as a preclinical model to study its effect on tumor growth and survival.