Grant: Operating Grant

While overall survival for children with cancer has improved substantially over the last 3 decades, significant challenges remain. Specifically, a considerable proportion of childhood cancers remains incurable, or can only be cured with treatments that leave a child with life-long mental or physical disabilities. In order to further improve survival, and the quality of life of children surviving high-grade astrocytomas, a particularly lethal and maiming form of brain cancer, it is important to understand what is driving this tumour type and inducing resistance. We identified Y-Box Protein 1 (YB-1) and Sorting nexin 3 (SNX3) to be abnormally highly present in these tumours and to be associated with worse outcome when present together. The ultimate aim of this comprehensive project is to gain insight into the function of YB1 and SNX3 and how they help drive tumour formation. We aim to identify targets and new therapies that may be developed for this particularly challenging disease. We will determine the gene signatures driven by aberrant YB-1 expression based on where it is present in the cell and uncover targets driven by this factor for new drug therapies. We will also uncover how SNX3 and YB-1 work together ad enhance tumour formation. These studies will provide an unprecedented view of YB-1/SNX3 functions and how best to counterbalance their effects. They will enable the development of new drugs, and offer the potential for tailored therapies for children with these presently lethal cancers who currently have limited options for clinical trials.