# Human Organoid Models for Pediatric High-Grade Gliomas

> **NIH NIH R21** · EMORY UNIVERSITY · 2023 · $430,375

## Abstract

Malignant pediatric high-grade gliomas (pHGGs), which infiltrate the brain and grow rapidly, are
a leading cause of cancer-related deaths in children. There is an urgent need for new
treatments for these tumors. Our research team and others have identified several related
fusion mutations in receptor tyrosine kinases (RTKs), such as MET, ALK, and NTRK, in pHGG
tumor cells. These mutations abnormally hyperactivate RTKs to cause pHGG cancer initiation
and progression. Up to 40% of pHGG tumors have these and similar RTK fusions. Several FDA-
approved specific tyrosine kinase inhibitors (TKIs) exist that target RTK mutations found in
pHGGs. However, treatment with TKIs is not sufficient to eliminate tumor cells in human
patients, despite compelling data from mouse models. Recent research has shown that human
neural cell types, including glia, display different developmental profiles, inflammatory
responses, and metabolic features and show greater developmental heterogeneity compared to
their murine counterparts. We predict that these differences may underlie human-specific
adaptations to TKIs and other RTK targeted therapies, particularly in the developing brain in
pediatric cancers. To test our hypothesis, we will Aim 1) create pHGG organoid models using
human patient-derived pHGG stem cells engrafted into human iPSC-derived brain organoid
cultures that approximate early postnatal human brain tissue, and Aim 2) model how
interactions between pHGG cells and the human neural microenvironment affect responses to
TKIs and other anti-tumor drugs. With our efforts, we hope to develop new humanized
experimental models for pHGG and to identify drug combinations that may be brought into
future clinical trials for this deadly disease.

## Key facts

- **NIH application ID:** 10727450
- **Project number:** 1R21NS133633-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Renee D Read
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $430,375
- **Award type:** 1
- **Project period:** 2023-09-11 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10727450

## Citation

> US National Institutes of Health, RePORTER application 10727450, Human Organoid Models for Pediatric High-Grade Gliomas (1R21NS133633-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10727450. Licensed CC0.

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