# Targeting purine biosynthesis to radiosensitize glioblastoma

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $68,185

## Abstract

Project Summary/Abstract
Glioblastoma (GBM) is the most common aggressive primary brain tumor and is uniformly fatal with a median
survival of around 1.5 years. Like surgery and chemotherapy, radiation (RT) is a critical treatment for nearly
every patient with GBM and has repeatedly improved patient survival in multiple randomized trials. Still, 80% of
GBMs recur within the high dose RT field. Thus, there is a critical need to develop strategies to overcome GBM
RT resistance to further improve patient outcomes.
GBM cells exhibit profound cancer-specific metabolic abnormalities, including elevated purine synthesis, to fuel
proliferation, invasion and survival. Using mice bearing intracranial orthotopic patient-derived brain tumors, my
research has established that the metabolic phenotype of elevated purine synthesis also mediates resistance to
RT in GBM by promoting the repair of RT-induced DNA damage. This purine-mediated RT resistance can be
overcome by treatment with mycophenolate mofetil (MMF), an FDA-approved and CNS-penetrant inhibitor of
purine biosynthesis.
In this research proposal I will determine how the RT response and purine synthesis regulate one another in
GBM. By employing a variety of cutting-edge metabolomic techniques and patient-derived GBM models, I will 1)
define the biosynthetic pathway GBMs use to generate purines, and 2) determine the RT response mechanism
by which GBMs increase purine levels to resist RT-induced DNA damage.
Findings from the experiments proposed here will expand our understanding of how tumors modulate
metabolism to promote therapeutic resistance, inform how to combine metabolic inhibitors with standard
therapies, and lay the mechanistic groundwork for clinical trials at the University of Michigan that targeting purine
biosynthesis to augment RT in GBM patients.

## Key facts

- **NIH application ID:** 10229208
- **Project number:** 1F32CA260735-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Andrew Joseph Scott
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,185
- **Award type:** 1
- **Project period:** 2021-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229208

## Citation

> US National Institutes of Health, RePORTER application 10229208, Targeting purine biosynthesis to radiosensitize glioblastoma (1F32CA260735-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10229208. Licensed CC0.

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