# Project 3: Inhibition of radiation-induced phenotype conversion in glioblastoma

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $345,841

## Abstract

Project 3: Inhibition of radiation-induced phenotype conversion in glioblastoma
SUMMARY/ABSTRACT
Despite a tremendous effort in basic science, clinical trials, drug development, and technical advances in
surgery and radiation oncology, glioblastoma remains incurable and improvements in overall survival have
been marginal. While radiotherapy is still one of the most effective treatment options for glioblastoma, it cannot
control the disease over time. This led us to conclude that novel combination therapies are desperately needed
to improve radiation treatment outcome for patients suffering from this disease. The studies outlined in this
proposal are based on a hypothesis that is backed by our extensive preliminary data and rigorous published
data in the literature. Specifically, we hypothesize that radiation causes a phenotype conversion of
differentiated glioma cells into therapy-resistant glioma-initiating cells (GICs), and that interfering with this
process will increase the efficiency of radiotherapy. The three aims of this study will address this aspect of
glioma biology using an innovative tool to track GICs and their progeny, while leveraging the unique resources
and expertise available in the proposed UCLA SPORE in Brain Cancer. In Aim 1, we will study spontaneous
and radiation-induced phenotype conversion in glioblastoma under different microenvironmental conditions,
and determine if this process generates tumorigenic GICs in vitro and in vivo. In Aim 2, we will attempt to
prevent phenotype conversion of non-tumorigenic cells into GICs using dopamine receptor antagonists.
Finally, in Aim 3, we propose a novel clinical trial to test whether quetiapine, a dopamine receptor antagonist,
can reduce the number of GICs in patients with recurrent GBM and prolong their survival. If successful, results
from these studies could have a wider impact on cancer, as these principles may apply not only to
glioblastoma but to many other solid tumors.

## Key facts

- **NIH application ID:** 10225552
- **Project number:** 5P50CA211015-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Frank Pajonk
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $345,841
- **Award type:** 5
- **Project period:** 2017-08-11 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225552

## Citation

> US National Institutes of Health, RePORTER application 10225552, Project 3: Inhibition of radiation-induced phenotype conversion in glioblastoma (5P50CA211015-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225552. Licensed CC0.

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