Targeting Signaling Between Glioblastoma and the Subventricular Zone Niche

TARGETING SIGNALING BETWEEN GLIOBLASTOMA AND THE SUBVENTRICULAR ZONE NICHE Glioblastoma (GBM) is the most malignant and proliferative primary brain tumor in adults. It remains a therapeutic challenge despite current treatment strategies that include surgery, radiation, and chemotherapy. Due to the tumor's high invasiveness, complete surgical resection is often impossible, leading to an almost 100% recurrence rate. Brain tumor initiating cells (BTIC), a subpopulation of undifferentiated cells within GBM, are responsible for tumor initiation and maintenance, exhibiting self-renewing and pluripotent properties in vivo, similar to those of Neural Progenitor Cells (NPC). Recent studies by our group and others have demonstrated that GBMs located in proximity to the lateral ventricles (LV) exhibit multiple factors that negatively impact patient survival, including increased proliferation and recurrence at distant locations. The underlying reasons for these worse outcomes in LV-proximal GBMs are not well understood but may involve the influence of the sub-ventricular zone (SVZ) neurogenic niche in the LV. Leveraging a GBM animal model that recapitulates the effects of LV-proximity on tumor malignancy, we have observed that neural progenitor cells (NPC) increase the proliferation and migration capacity of GBM-derived BTIC. Additionally, using image-guided biopsies of brain tumor samples in patients, we have identified intratumoral transcriptional differences induced by LV-proximity. Thus, we propose to investigate the specific protein components that drive the increased malignancy of LV-proximal tumors, utilizing novel cell-specific proteomic and transcriptomic approaches. The completion of this study will enhance our understanding of the mechanisms underlying the interaction between brain tumors and the neurogenic niche in the SVZ. Ultimately, our findings will identify novel therapeutic targets to improve the survival of patients with GBM.