# Characterization of the cellular mechanisms of radiation induced brain necrosis for clinical intervention

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $174,886

## Abstract

Project Summary/Abstract
Cure rates for childhood cancers have improved. Unfortunately, many survivors now live with life-long side
effects from treatment itself. Radiation therapy, used for brain tumors, is particularly damaging. The most
serious side effect is necrosis which can result in weakness, paralysis or even death. Proton therapy is an
increasingly popular radiation modality. Proton therapy reduces exposure to normal tissues and the reby
may decrease the incidence of cognitive deficits following radiation. However, recent studies, including our
own suggest that certain areas of proton beams may be more damaging to brain tissue than others
potentially leading to higher rates of necrosis. Here we will develop high accuracy models to correlate
necrosis with the physical parameters of proton beams. These models will include multi-cell type human
brain “organoids” as well as rodent animal models. Using these models as well as clinical data, we will
identify the physical factors of proton therapy which may lead to necrosis. This is significant in that this data
may be used to design safer proton therapy treatments in which the most biologically effective portions of
beams are solely placed within the tumor. This should reduce necrosis and improve disease control. In a
second component of our study, we will examine the molecular mechanisms of necrosis. Rather than being
simple dis-organized death, we will determine if radiation induces an orderly programmed cell death
pathway. We will conduct the following aims; (1) relate the physical factors of proton beams with biological
response, (2) explore the cellular and molecular mechanisms of radiation induced brain damage and (3)
validate the clinical consequences of variability in the effectiveness of proton beams. The knowledge gained
will quickly influence the treatment of brain tumor patients and expedite the clinical introduction of agents
and approaches to combat the negative effects of radiation on the brain.

## Key facts

- **NIH application ID:** 10891587
- **Project number:** 5R01CA255596-04
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** DAVID R GROSSHANS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $174,886
- **Award type:** 5
- **Project period:** 2021-08-02 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891587

## Citation

> US National Institutes of Health, RePORTER application 10891587, Characterization of the cellular mechanisms of radiation induced brain necrosis for clinical intervention (5R01CA255596-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10891587. Licensed CC0.

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