# Targeting epigenetic remodeling factors to radiosensitize glioblastoma

> **NIH NIH R03** · OHIO STATE UNIVERSITY · 2020 · $78,000

## Abstract

PROJECT SUMMARY / ABSTRACT
Glioblastomas (GBM) are the most common primary brain tumor and the most lethal. Conventional therapy
of surgical resection followed by the combination of radiation and chemotherapy and adjuvant chemotherapy
offers only palliation and recurrence is nearly universal. The failure of this approach is due to numerous factors
that ultimately promote therapeutic resistance of the tumor. One underlying cause of therapeutic resistance is
a subpopulation of cells within GBM called cancer stem-like cells (CSCs) that harbor the more malignant
properties of GBM and drive the growth of these tumors. Our overall objective is to elucidate points of fragility
for CSCs and develop effective treatment modalities that will inclusively target this tumor-propagating subset
of cells. To this end, we have identified a new therapeutic strategy that utilizes the small molecule curaxin-137
which targets a key DNA modification protein (facilitates chromatin transcription, FACT). We previously
demonstrated that disruption of FACT function attenuated key CSC characteristics. Our more recent
preliminary data demonstrated that disruption of FACT increased the amount of DNA damage in CSCs and
reduced cell viability when combined with radiotherapy. We hypothesize that FACT is a key mediator of the
CSC phenotype and a viable therapeutic target that will reduce tumor growth when combined with
radiotherapy. Based on this background and preliminary data we propose to, 1) investigate if perturbation of
FACT activity enhances the efficacy of radiation by direct alteration of the DNA damage response and, 2)
test if inhibition of FACT decreases the radioresistance phenotype of CSCs in vivo and if it can enhance to
in vivo efficacy of radiotherapy. These studies will investigate a combination therapeutic approach using a
clinically relevant inhibitor that alters the ability of CSCs to drive tumorigenesis, ultimately reducing tumor
growth, which can be rapidly integrated into GBM therapy. Moreover, successful execution of this scientific
endeavor promises to bring important new insights to the overall cancer biology community.

## Key facts

- **NIH application ID:** 9842616
- **Project number:** 5R03CA227206-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Monica Venere
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,000
- **Award type:** 5
- **Project period:** 2019-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842616

## Citation

> US National Institutes of Health, RePORTER application 9842616, Targeting epigenetic remodeling factors to radiosensitize glioblastoma (5R03CA227206-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9842616. Licensed CC0.

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