# Impact of radiation-induced senescence on the glioblastoma microenvironment

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2020 · $199,512

## Abstract

PROJECT SUMMARY
Radiation therapy is standard management for glioblastoma (GBM); however, these tumors invariably recur,
frequently in a more aggressive and treatment-resistant manner than the original tumor. Radiation is known to
induce alterations correlated with mesenchymal tumor subtype. However, the mechanisms by which the
radiated microenvironment may exacerbate recurrent tumor behavior remain Ill-defined. Cell senescence is
induced by radiation and given pro-inflammatory and ECM-altering factors secreted by senescent cells, may
contribute to worsened GBM behavior in the previously radiated brain.
• Our long-term goal is to understand the contribution of the radiated tumor microenvironment, including that
 of senescent cells to facilitate tumor recurrence.
• The objective of these proposed activities is to evaluate the generalizability and reproducibility of radiation-
 induced pro-tumorigenic impacts across multiple parameters of radiation dose, cell type, and model, and to
 interrogate the role of senescent cells in this process.
• Our central hypothesis is that brain radiation alters the brain microenvironment, including via induction of
 cellular senescence, to increase tumor aggressiveness.
• The specific aims of this proposal are: (Aim 1) to rigorously test if prior radiation exposure induces more
 aggressive tumor behavior across radiation schemas, GBM models and post-radiation time-points; (Aim 2)
 to test if senescent cells in the glioblastoma microenvironment increase tumor aggressiveness, using gain
 and loss of function experiments with senescent cell implantation and pharmacologic and genetic ablation
 of senescent cells. As an experimental sub-aim, we will test using Single nucleus-RNAseq if transcriptional
 changes of senescence are induced in a specific stromal cell types, and whether or not these correlate with
 induction of a mesenchymal signature in implanted tumor cells.
With advances in senolytic therapies, this work may provide an avenue to attenuate unintended deleterious
sequelae of radiation therapy on the tumor microenvironment. Moreover, given the de-novo emergence of
senescence in GBM, senolytic therapies may provide an avenue to attenuate GBM progression both in
synergy with, and independently of brain radiation.

## Key facts

- **NIH application ID:** 9843747
- **Project number:** 5R21NS109770-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Terry Burns
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,512
- **Award type:** 5
- **Project period:** 2019-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843747

## Citation

> US National Institutes of Health, RePORTER application 9843747, Impact of radiation-induced senescence on the glioblastoma microenvironment (5R21NS109770-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9843747. Licensed CC0.

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