Grant: Travel Awards - Institute Community Support

Glioblastomas are the most common and aggressive type of brain cancer. Despite the best treatments available (surgery, radiation, and chemotherapy), the majority of patients survive for just over one year before passing from this incurable disease. Presently, therapies fail to eliminate glioblastoma stem cells allowing them to grow uncontrollably and drive cancer relapse thus we must target these cancer stem cells to make any notable improvement in patient outcomes. Current research suggests that cancer stem cells in glioblastoma arise from dysfunctional stem cells from a unique region in the brain called the subventricular zone. During fetal development, stem cells from the subventricular zone are the origin of the human brain, but in cancer, this developmental process is hijacked. Normally, molecular regulatory signals in the subventricular zone keep stem cell division tightly controlled but in glioblastoma, this regulation is disrupted. By comparing normal brain stem cells and cancer stem cells in their respective tissue environments, we have found key regulatory signals exploited by cancer stem cells for their survival. Our work highlights the potential for therapies to target dysfunctional cancer stem cell signalling pathways to effectively treat glioblastoma. Here we evaluate treatments using glioblastoma organoids (miniature tumors) grown from patient tissues with the aim of restoring brain stem cell regulation. The mechanism of successful treatments was further interrogated by genetically sequencing individual cells from these treated tumor organoids to understand changes in cell state and tumor interactions. We are confident this work will bring us one step closer to finding effective treatments for glioblastoma and are well poised to launch a clinical trial to benefit thousands of patients.