# Screening for DNA damage response modulators in glioblastoma stem cells

> **NIH NIH R61** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $420,000

## Abstract

Abstract
There is presently no cure for high grade gliomas which are associated with a bleak prognosis
and a poor quality of life. GBM patients typically undergo surgical resection followed by radiation
therapy (RT) combined with the alkylating agent temozolomide (TMZ). However, virtually all GBM
patients either fail to respond to this treatment, or ultimately develop resistance, underlining the
urgency for effective adjuvant therapies. Both RT and TMZ can target tumor cells by causing
lethal DNA double-strand breaks, which could be recognized and repaired by the intrinsic DNA
damage response (DDR) thus protecting against DNA damage-induced cell death. Further, GBMs
are enriched in a subset population of glioma cancer stem cells (GSCs), characterized by an
upregulated DDR which contributes to their superior therapeutic resistance. Targeting DNA repair
can increase/restore sensitivity of brain tumors to TMZ and RT, thus increasing therapeutic
efficacy and minimizing tumor recurrence. We have designed a rapid, versatile and highly
sensitive reporter that can detect and quantify minute amounts of DNA double-strand break
repairs such as homology-directed repair as well as non-homologous end joining without
disrupting cells. Here we propose to use this reporter in order to identify modulators of DNA
damage repair in GSCs. In Aim 1 (R61 phase), we will develop and optimize a high-throughput
screening assay to monitor DDR in GSCs. In Aim 2 (R33 phase), we will use this assay to screen
for compounds which inhibit DNA damage repair. Upon completion of this project, this screen
should identify novel compounds which effectively sensitize GSCs to chemoradiotherapy and
increase the efficacy of genotoxic therapeutics.

## Key facts

- **NIH application ID:** 10038588
- **Project number:** 1R61NS117554-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Christian Elias Badr
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038588

## Citation

> US National Institutes of Health, RePORTER application 10038588, Screening for DNA damage response modulators in glioblastoma stem cells (1R61NS117554-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10038588. Licensed CC0.

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