# Development of Advanced Preclinical Models for Pediatric Solid Tumors

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $601,492

## Abstract

PROJECT SUMMARY
Pediatric solid tumors are a rare and highly heterogeneous collection of cancers. For many subtypes, progress
in defining novel therapies has stalled over the last 10-20 years. Indeed, for most of these tumors
chemotherapy continues to be the primary form of treatment and targeted therapies are not available. This
lack of progress is likely due at least in part to the difficulty in developing clinical trials for individual histologic
subtypes given their rarity. An alternative is to develop a robust preclinical testing program. Currently, such
programs are limited by the lack of well-credentialed models that incorporate the most advanced technologies
for genomic and functional characterization and do to the lack of good models for therapy-resistant and
metastatic disease. Here we bring together two PIs with complimentary expertise to develop new approaches
for validation and preclinical use of pediatric solid tumor animal models. Our focus is on the use of patient-
derived xenografts for three most common histotypes: osteosarcoma, ewing sarcoma and rhabdomyosarcoma.
PDX models are particularly well suited for studying highly heterogeneous tumors such as pediatric solid
tumors. In Aim 1, we will develop novel advance PDX models that incorporate two key innovations: i) utilization
of CRISPR/CAS9 technology for genetic interrogation and ii) autologous and allogeneic approaches for
development of PDX models with a human immune system (hu-PDX). In Aim 2, we will develop novel
computational tools to assess the similarity of PDX models to their tumor of origin and to evaluate human-
mouse and mouse-mouse evolution which may impact clinical relevance. We will work closely with members of
the Oncology Models Forum to develop scoring systems to assess this similarity and make these tools widely
available to the modeling community. In Aim 3, we will evaluate intratumor heterogeneity during human-mouse
and mouse-mouse evolution of PDX models using single cell RNAseq. We expect that the tools and models
developed here will be widely applicable to other PDX models and that the specific models we develop will
help facilitate preclinical research. We will make all tools and models widely accessible to the research
community.

## Key facts

- **NIH application ID:** 10120656
- **Project number:** 5R01CA243555-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** DAVID H HAUSSLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $601,492
- **Award type:** 5
- **Project period:** 2020-03-05 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120656

## Citation

> US National Institutes of Health, RePORTER application 10120656, Development of Advanced Preclinical Models for Pediatric Solid Tumors (5R01CA243555-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10120656. Licensed CC0.

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