# Project 2: Molecular and Clinical Inputs Affecting Optimization of Glioma Therapy

> **NIH NIH U54** · DANA-FARBER CANCER INST · 2020 · $126,492

## Abstract

Project 2: Molecular and clinical inputs affecting optimization of glioma therapy 
Project Summary / Abstract: 
Glioblastomas (GBM) are the most malignant and common of the primary brain tumors and are divided into 
several molecular subgroups denoted PN-GBM, MES-GBM and CL-GBM. Because of a subset of cells with 
stem-like properties, these tumors are relatively insensitive to DNA damaging agents, such as radiation (XRT), 
and are consequently highly resistant to therapy. In PN-GBM the stem-like cells live adjacent to blood vessels, 
in the perivascular niche (PVN). In other GBM subtypes, stem-like cells are distributed throughout the tumors. 
In order to identify better GBM therapies, we need to improve our understanding of the biology of stem- and 
non-stem-like GBM cells as a function of molecular subtype. We have previously demonstrated that the 
dynamic inter-conversion of these two cell types occurs within hours of therapy and can be successfully 
mathematically modeled, providing a basis for optimizing radiation schedules to maximize survival in mouse 
models of PN-GBM. However, optimum radiation administration schedules for other GBM subtypes are 
unknown. Additionally, standard of care calls for the administration of adjuvant temozolomide (TMZ) 
concurrently with radiation. Based on our preliminary data, we hypothesize that (1) a mathematical model of 
radiation and TMZ response in MES-GBM will be different than that for PN-GBM, (2) a mathematical model of 
radiation and TMZ response in MES-GBM will be different than that for PN-GBM, (3) there are biological 
characteristics of GBM that, if altered, would fundamentally enhance the responses of all GBMs regardless of 
subtype. We propose three specific aims to test these hypotheses: Aim 1: Improve our understanding of the 
PVN in PN-GBM and use this understanding to optimize combined TMZ/XRT therapy. Aim 2: Create a 
mathematical model of radiation response in MES-GBM where the stem cells are more evenly distributed. Aim 
3. Identify strategies that would improve the standard of care for all GBM regardless of subtype. Our goal is to 
translate our findings into future clinical trials.

## Key facts

- **NIH application ID:** 10134500
- **Project number:** 3U54CA193461-05S1
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Eric C. Holland
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $126,492
- **Award type:** 3
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134500

## Citation

> US National Institutes of Health, RePORTER application 10134500, Project 2: Molecular and Clinical Inputs Affecting Optimization of Glioma Therapy (3U54CA193461-05S1). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/10134500. Licensed CC0.

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