# In vivo Drug Testing of Pediatric CNS Tumors Using Patient Derived Orthotopic Xenograft Models

> **NIH NIH U01** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2022 · $608,784

## Abstract

This application is prepared in response to the funding opportunity: NCI Pediatric In Vivo Testing Program
(U01), RFA-CA-20-034 to renew our existing PPTC UO1 grant. Specifically, we propose to continue the in vivo
testing program for central nervous system (CNS) tumors using our panel of patient derived orthotopic xenograft
(PDOX) models. Brain tumor is the leading cause of cancer-related death in children. One of the challenges
in clinical drug development is how to effectively prioritize drug candidates to ensure clinical success in
cancer patients. However, efforts in identifying new anti-cancer agents for that are most likely to be effective
in the clinic have been blocked for many years due to the lack of clinically relevant and molecularly
accurate model system. Fortunately, we have established a panel of 150 PDOX models of pediatric brain
tumors through direct injection of patient tumor specimens into the brains of SCID mice. These PDOX models
are shown to have replicated the histopathology and major genetic abnormalities of the original patient
tumors even during serial sub-transplantations in vivo in mouse brains. They not only represent different
clinical stage (i.e., at diagnosis, relapse and terminal/autopsy) but also replicate a broad spectrum of the newly
identified molecular subtypes of nearly all types of pediatric brain tumors. The xenograft tumor cells can also
be cryopreserved for sustained and on-demand supply of tumorigenic PDOX cells. This capacity combined
with our optimized surgical procedure, with which we can implant up to 260 mice per day, makes it possible for
us to test multiple (e.g., 6-10) drugs per year for every tumor type. Our objective is therefore to make use of
this unique panel of PDOX models to examine therapeutic efficacy of new agents and to analyze mechanisms
of action and therapy resistance in high grade glioma, medulloblastoma, ependymoma, DIPG and ATRT. Our
hypothesis is that these patient-specific PDOX tumors will respond to anti-cancer therapies similarly to the
corresponding human primary tumors, and the effective agents identified through this system would have
better chances of clinical success. To test this hypothesis, we will perform a series of in vitro and in vivo
assays to achieve the following aims: 1) to identify genetically accurate candidate PDOX models that bear
the therapeutic target(s) of new investigational drugs through data mining of our mouse model molecular
characterization databases; 2) to select the most responsive models through functional in vitro screening to
determine time- and dose-responses; 3) to demonstrate therapeutic efficacy of new investigational drugs
in multiple target-bearing PDOX models; and 4) to perform detailed analysis of cellular and molecular
mechanisms of cell killing as well as the causes of therapy resistance both in vitro and in vivo. Our novel
panel of PDOX mouse models represents a broad spectrum of genetic abnormalities of pediatric CNS
tumors. All ...

## Key facts

- **NIH application ID:** 10437004
- **Project number:** 5U01CA199288-07
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Xiaonan Li
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $608,784
- **Award type:** 5
- **Project period:** 2015-07-14 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437004

## Citation

> US National Institutes of Health, RePORTER application 10437004, In vivo Drug Testing of Pediatric CNS Tumors Using Patient Derived Orthotopic Xenograft Models (5U01CA199288-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10437004. Licensed CC0.

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