# Utilizing Radiation-Induced Multi-potency to Increase the Efficacy of Radiotherapy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $484,078

## Abstract

SUMMARY/ABSTRACT
Radiation therapy (RT) is an integral part of the standard-of-care against glioblastoma (GBM).
While the addition of RT to surgery over surgery alone significantly prolongs patient survival, all
patients with GBM ultimately succumb to the disease and survival times are unacceptably low.
So far, the addition of targeted or non-targeted therapies to surgery and RT have had limited
success and indicate the need for novel strategies against this disease.
There is ample evidence supporting the heterogeneity of GBM and the existence of a small
population of glioblastoma stem cells (GSCs)), relatively resistant to RT and chemotherapy, and
able to regrow the tumor. Together, treatment resistant GSCs, dispersion of cancer cells beyond
the visible tumor, large areas of hypoxia and the blood-brain-barrier (BBB) add to the challenge
GBM presents to cancer therapy.
We have previously demonstrated that radiation reactivates stem cell programs causing cellular
multipotency and plasticity, followed by the acquisition of an induced GSC state. Importantly, we
showed that this process could be targeted and that preventing the induction of GSCs led to
improved survival in animal models of GBM. We have now developed novel compounds that
cross the BBB and prevent the radiation-induced generation of GSCs. Furthermore, our
preliminary data indicate that a radiation-induced multipotent state can be utilized to allow for
terminal differentiation of GBM cells. The studies proposed in this application build on these
findings and take the research program into this exciting new direction to utilize this induced
multipotent state for altering the radiation responses of GBM.

## Key facts

- **NIH application ID:** 10844584
- **Project number:** 5R01CA281682-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Frank Pajonk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $484,078
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844584

## Citation

> US National Institutes of Health, RePORTER application 10844584, Utilizing Radiation-Induced Multi-potency to Increase the Efficacy of Radiotherapy (5R01CA281682-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10844584. Licensed CC0.

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