# Selective Targeting of Glioma Stem Cells Through Sema3C/PlexinD1

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $346,719

## Abstract

   
DESCRIPTION (provided by applicant) Glioblastoma is an incurable primary brain tumor. Glioma stem cells (GSCs) are a subpopulation of cells that resist standard therapy to contribute to disease progression. Identification of new GSC-specific targets may facilitate the development of novel therapeutics. We have found that GSCs appropriate an evolutionary conserved neurodevelopmental program to promote their tumorigenicity. GSCs utilize Sema3C/PlexinD1 to promote the defining features of GSCs: survival, self-renewal, invasion and radioresistance. Importantly, neural progenitor cells do not use this pathway, suggesting that inhibition of Sema3C/PlexinD1 will have a high therapeutic index. We now guide the clinical translation of Sema3C/PlexinD1 into the clinic. Our central hypothesis is that GSCs use Sema3C/PlexinD1 to promote their own self- renewal and that Sema3C/PlexinD1 serve as important prognostic biomarkers and therapeutic targets. In Aim 1, we will use our large GBM specimen collection to assess the prevalence of Sema3C/PlexinD1 receptor in GBM and test the prognostic value of Sema3C in long and short-term survivors of GBM. In Aim 2, we will determine the role of Sema3C/PlexinD1 in regulating Wnt/β-catenin signaling. In Aim 3, we will provide proof- of-principle that targeting the Sema3C/PlexinD1 signaling axis in combination with radiation improves survival in mouse models of glioblastoma. If successful, these findings will lead to a prospective clinical trial assessing Sema3C as a prognostic biomarker and guide the development of novel therapeutics targeting Sema3C/PlexinD1.

## Key facts

- **NIH application ID:** 9900879
- **Project number:** 5R01NS092641-05
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Jennifer S Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,719
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900879

## Citation

> US National Institutes of Health, RePORTER application 9900879, Selective Targeting of Glioma Stem Cells Through Sema3C/PlexinD1 (5R01NS092641-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900879. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*