# Determining the optimal ion and fractionation scheme for the treatment of GBM in a comprehensive human organoid model

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $486,226

## Abstract

PROJECT SUMMARY/ABSTRACT
Radiation plays a central role in the management of the most lethal central nervous system malignancy,
glioblastoma (GBM), yet local control rates, and hence survival, remain dismal for this disease. Even novel
therapies, such as immunotherapy, have not shown efficacy in the treatment of GBM. Meanwhile, radiation
dose escalation studies have demonstrated improved local control. However, dose escalated treatments are
hindered by the increased incidence of radiation induced brain necrosis in surrounding tissues. High LET
particle therapy holds the potential to both increase tumor cell kill and decrease normal tissue toxicity, yet
the data required to develop models for clinical treatments regarding the biological effectiveness of high LET
beams on normal brain tissue and GBM cells is sparse. This fact is especially true when considering results
reported utilizing the appropriate environment for the origination and growth of GBM cells – the human
brain. We have implemented recently developed high accuracy models which are truly beginning to
recapitulate the native GBM niche in order to correlate both necrosis induction and progression and tumor
cell response with the physical parameters of particle beams. These models include multi-cell type human
brain organoids (cerebral organoids) as well as immune-competent orthotopic rodent models. Using these
models, we will identify the physical factors of particle beams which may lead to necrosis. This is significant
in that this data will aid the design of safer treatments by reducing necrosis and improving disease control.
In the second component of our study, we will examine the molecular mechanisms of necrosis and
neuroinflammation. Rather than being a simple accidental, disorganized death, we will determine if radiation
induces an orderly programmed cell death pathway. Overall, we will conduct the following aims; (1) identify
the optimal particle and fractionation for treatment of GBM, (2) explore the cellular and molecular
mechanisms of radiation induced brain damage, and (3) develop biological effect models for clinical use.
The knowledge gained will quickly influence the treatment of brain tumor patients and expedite the clinical
introduction heavy ion therapy for glioblastoma.

## Key facts

- **NIH application ID:** 10130746
- **Project number:** 1R01CA256848-01
- **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:** 2021
- **Award amount:** $486,226
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130746

## Citation

> US National Institutes of Health, RePORTER application 10130746, Determining the optimal ion and fractionation scheme for the treatment of GBM in a comprehensive human organoid model (1R01CA256848-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130746. Licensed CC0.

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