# TARGETING SIGNALING BETWEEN GLIOBLASTOMA AND THE SUBVENTRICULAR ZONE NICHE

> **NIH NIH R01** · MAYO CLINIC  JACKSONVILLE · 2024 · $449,203

## Abstract

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.

## Key facts

- **NIH application ID:** 10918651
- **Project number:** 1R01NS137907-01
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** Hugo Guerrero-Cazares
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $449,203
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918651

## Citation

> US National Institutes of Health, RePORTER application 10918651, TARGETING SIGNALING BETWEEN GLIOBLASTOMA AND THE SUBVENTRICULAR ZONE NICHE (1R01NS137907-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10918651. Licensed CC0.

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