therapeutic targeting of OLIG2 in high grade glioma

CT-179 is a world first, small molecule drug designated for specific targeting of a transcription factor named OLIG2. This thesis investigates the working mechanism and efficacy of CT-179 for the treatment of the most malignant brain tumour, glioblastoma. Mechanistically, CT-179 inhibits OLIG2 biological function through destabilizing its interaction with target DNA, and induces significant tumour cell death in cell lines. In the zebrafish and mouse models of glioblastoma, CT-179 can penetrate the blood-brain barrier, and significantly reduce tumour burden. Importantly, it shows enhanced anti-tumour activity when used in combination with standard of care radiotherapy and temozolomide, suggesting that CT-179 could be added to the current standard of care treatment to improve patient outcome. These studies demonstrates that the pharmacological inhibition of OLIG2 is a promising treatment strategy for glioblastoma that warrants rapid translation into the clinic.