# SPORE: Targeted Therapies for Glioma - Diversity Supplement

> **NIH NIH P50** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $264,010

## Abstract

Abstract
Glioblastoma is the most common and the most malignant primary brain tumor with a
median life expectancy of 15 months despite multimodal therapy. Its aggressive nature
is in part due to its ability to escape immune surveillance and to redundant cell signaling
that makes it resistant to single-agent targeted therapies. The cyclin D1-CDK4/6-
retinoblastoma signaling axis has been implicated in cancer immune evasion and
resistance to receptor tyrosine kinase inhibition in multiple cancers. As this axis is
deregulated in 80% of glioblastoma, there is ongoing research into whether inhibition of
CDK4/6 sensitizes glioblastoma to immunotherapy. This project builds on this work by
exploring the role of the epigenetic machinery that is downstream of CDK4/6 signaling
on glioblastoma immune evasion, as well as the role of CDK4/6 signaling on resistance
to EGFR inhibition. To that end, we will determine whether inhibition of the polycomb
repressor complex 2 (PRC2) or of the DNA methyltransferases (DNMTs) triggers tumor
cell-intrinsic anti-tumor immunity, and whether PRC2 or DNMT inhibitors synergize with
immune checkpoint blockade in novel immunocompetent patient-derived models of
glioblastoma. We will also determine whether combination EGFR and CDK4/6 inhibition
synergize in a genetically engineered mouse model of glioblastoma driven by EGFRvIII,
the most common EGFR mutation in human glioblastoma. We hope that this work will
uncover rational combinations of targeted therapies or targeted therapies with
immunotherapy that will serve as new therapeutic strategies for patients with
glioblastoma.

## Key facts

- **NIH application ID:** 10136362
- **Project number:** 3P50CA165962-07S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Tracy T Batchelor
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $264,010
- **Award type:** 3
- **Project period:** 2013-09-19 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136362

## Citation

> US National Institutes of Health, RePORTER application 10136362, SPORE: Targeted Therapies for Glioma - Diversity Supplement (3P50CA165962-07S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10136362. Licensed CC0.

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