Development of Advanced Preclinical Models for Pediatric Solid Tumors

儿科实体瘤先进临床前模型的开发

基本信息

项目摘要

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.
项目总结

项目成果

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DAVID H HAUSSLER其他文献

DAVID H HAUSSLER的其他文献

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{{ truncateString('DAVID H HAUSSLER', 18)}}的其他基金

Data Resource and Administrative Coordination Center for the Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes Consortium
精神科和神经发育障碍风险基因联盟的可扩展和系统神经生物学数据资源和行政协调中心
  • 批准号:
    10642251
  • 财政年份:
    2023
  • 资助金额:
    $ 58.95万
  • 项目类别:
Enhance UCSC Xena: extend interactive visualization to ultra-large-scale multi-omics data and integrate with analysis resources
增强 UCSC Xena:将交互式可视化扩展到超大规模多组学数据并与分析资源集成
  • 批准号:
    10687189
  • 财政年份:
    2021
  • 资助金额:
    $ 58.95万
  • 项目类别:
Center for Live Cell Genomics
活细胞基因组学中心
  • 批准号:
    10307037
  • 财政年份:
    2021
  • 资助金额:
    $ 58.95万
  • 项目类别:
Enhance UCSC Xena: extend interactive visualization to ultra-large-scale multi-omics data and integrate with analysis resources
增强 UCSC Xena:将交互式可视化扩展到超大规模多组学数据并与分析资源集成
  • 批准号:
    10187394
  • 财政年份:
    2021
  • 资助金额:
    $ 58.95万
  • 项目类别:
Enhance UCSC Xena: extend interactive visualization to ultra-large-scale multi-omics data and integrate with analysis resources
增强 UCSC Xena:将交互式可视化扩展到超大规模多组学数据并与分析资源集成
  • 批准号:
    10430132
  • 财政年份:
    2021
  • 资助金额:
    $ 58.95万
  • 项目类别:
Center for Live Cell Genomics
活细胞基因组学中心
  • 批准号:
    10676332
  • 财政年份:
    2021
  • 资助金额:
    $ 58.95万
  • 项目类别:
Nanoparticle Tracking Analyzer (NTA) for the Center for Live Cell Genomics
用于活细胞基因组学中心的纳米颗粒跟踪分析仪 (NTA)
  • 批准号:
    10817569
  • 财政年份:
    2021
  • 资助金额:
    $ 58.95万
  • 项目类别:
Enabling Comparative Pangenomics
实现比较泛基因组学
  • 批准号:
    10555318
  • 财政年份:
    2020
  • 资助金额:
    $ 58.95万
  • 项目类别:
Development of Advanced Preclinical Models for Pediatric Solid Tumors
儿科实体瘤先进临床前模型的开发
  • 批准号:
    10356873
  • 财政年份:
    2020
  • 资助金额:
    $ 58.95万
  • 项目类别:
Center for Big Data in Translational Genomics
转化基因组学大数据中心
  • 批准号:
    9277519
  • 财政年份:
    2014
  • 资助金额:
    $ 58.95万
  • 项目类别:

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