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
- 批准号:10579262
- 负责人:
- 金额:$ 58.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-03-05 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAdvanced DevelopmentAllogenicAlveolarAnimal ModelAutologousBiologicalBiological ModelsCRISPR screenCRISPR/Cas technologyCellsChildhood Solid NeoplasmClinicalClinical TrialsClonal EvolutionCollaborationsCollectionCombined Modality TherapyCommunitiesComputational BiologyComputing MethodologiesCredentialingData SetDevelopmentDiseaseDrug TargetingDrug resistanceEnvironmentEvolutionEwings sarcomaGene ClusterGene ExpressionGenerationsGenesGeneticGenetic TranscriptionGenomic approachGenomicsGoalsHeterogeneityHistologicHumanImmuneImmune systemImmunocompetentImmunocompromised HostImmunogenomicsIndividualMalignant Childhood NeoplasmMalignant NeoplasmsMammalian CellMethodsModelingMolecularMusOncologyPathway interactionsPatientsPediatric OncologistPhenotypePre-Clinical ModelPreclinical TestingPrimary NeoplasmRare DiseasesReagentResearchResearch PersonnelResistanceResolutionRhabdomyosarcomaSystemTechnologyTestingTranslatingValidationWorkcancer genomicscandidate identificationchemotherapyclinical careclinically relevantcomputerized toolsdata sharingdrug testingearly phase clinical trialfunctional genomicsgenetic analysisgenetic technologygenome sequencinggenomic toolsinnovationmembermodel developmentnovelnovel strategiesnovel therapeuticsosteosarcomapatient derived xenograft modelpediatric patientspre-clinicalpre-clinical researchpreclinical developmentprogramsresponsesingle-cell RNA sequencingtargeted treatmenttherapy designtherapy resistanttooltranscriptome sequencingtranslational scientisttreatment responsetumortumor heterogeneitywhole genome
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
期刊论文数量(0)
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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:
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:
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:
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:
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