NCI Pediatric In Vivo Testing Program: Neuroblastoma
NCI 儿科体内测试项目:神经母细胞瘤
基本信息
- 批准号:10437913
- 负责人:
- 金额:$ 69.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAdolescentAdrenocortical carcinomaAdultAllograftingAntineoplastic AgentsBiological AssayBiological MarkersCaringCause of DeathCessation of lifeChemotherapy and/or radiationChildChild DevelopmentChildhoodClinicClinicalClinical TrialsClinical Trials DesignCollaborationsCollectionCommunitiesCoupledDataDevelopmentDiagnosisDiseaseDisease modelDrug ModelingsDrug TargetingFoundationsFundingGenetic FingerprintingsGenetic Predisposition to DiseaseGenomicsGliomaGoalsHealthImmunooncologyImmunotherapeutic agentImmunotherapyIn VitroIndustryInflammatory PseudotumorInfrastructureKi-1 Large-Cell LymphomaKnowledgeLeadershipMYCN geneMalignant Childhood NeoplasmMalignant NeoplasmsMeasurableMissionModelingModernizationMolecularMorbidity - disease rateMusNational Cancer InstituteNeoplasm MetastasisNeuroblastomaOncogenicPatient MonitoringPatient SelectionPatientsPediatric OncologyPharmaceutical PreparationsPharmacologyPhasePlayPositioning AttributePre-Clinical ModelPreclinical TestingPublic HealthRadiation therapyReagentRecurrent diseaseRelapseResearchResource SharingResourcesRoleSamplingSeriesSolidSolid NeoplasmSurvivorsTechnologyTestingTherapeuticTherapeutic InterventionTherapeutic TrialsToxic effectTranslatingTreatment FailureUnited States National Institutes of HealthWorkanticancer researchbasebiomarker-drivenchemotherapyclinical developmentcompanion diagnosticsdesigndisorder riskdrug testingearly phase clinical trialevidence basehigh riskhuman modelimprovedimproved outcomein vivoin vivo evaluationindividualized medicineinfancyinnovationmelanomamouse modelnext generation sequencingnovelnovel therapeuticspatient biomarkerspatient derived xenograft modelpre-clinicalpreclinical trialprogramspublic-private partnershiprare conditionrational designrefractory cancerresponsescreeningtargeted treatmenttherapy designtooltranslational research programtumor
项目摘要
Project Summary
Children with disseminated neuroblastoma have a very high risk of treatment failure and death despite
receiving intensified chemotherapy, radiation therapy and immunotherapy. The long-term goal of the Mossé
and Maris translational research programs is to substantively improve neuroblastoma cure rates by developing
patient-specific therapies that target the unique oncogenic drivers of each case. Within the context of the
National Cancer Institute’s Pediatric In Vivo Testing Program (Ped-In Vivo-TP) we propose a Neuroblastoma
Research Program built on richly annotated and highly characterized patient derived xenograft (PDX) and
other recently developed murine models of this disease. The central hypothesis to be tested in this Program is
that neuroblastoma-specific oncogenic drivers and optimal immunotherapeutic targets can be defined and
exploited through rationally designed therapies based on validated and clinically measurable biomarkers.
Through our dedicated focus on neuroblastoma and our central role in the former Pediatric Preclinical Testing
Program and Consortium, we have developed an investigative team and rich set of resources and reagents to
be uniquely positioned to achieve the goals of the Ped-In Vivo-TP. Here we propose to use a large (and
growing) collection of PDX models that have been fully characterized with the most modern genomic
technologies to address the challenge of prioritizing the large armamentarium of anti-cancer agents in
development so that early phase biomarker-driven clinical trials can be designed with the objective of showing
potent and specific anti-tumor activity. We propose three specific aims directed towards 1) developing and
characterizing highly annotated models of human neuroblastoma; 2) performing preclinical trials with drugs
directed against defined therapeutic vulnerabilities in order to prioritize agents for the clinic, and 3) developing
the portfolio of preclinical data required for design of clinical trials with robust biomarkers for patient selection
and monitoring. In collaboration with other preclinical testing programs, we will seek to determine if discoveries
in our program are relevant to other childhood cancers and collaborate across disease groups on clinical
development strategies. Thus, this Program will seek to shift the paradigm for how high-risk neuroblastoma
patients are treated with the goal of substantively improving the outcomes, both in terms of cure rates, but also
by decreasing the toxicity associated with current standards of care.
项目概要
尽管患有播散性神经母细胞瘤的儿童治疗失败和死亡的风险非常高
接受强化化疗、放射治疗和免疫治疗是Mossé的长期目标。
和 Maris 转化研究计划旨在通过开发显着提高神经母细胞瘤治愈率
针对每个病例独特的致癌驱动因素的患者特异性治疗。
美国国家癌症研究所的儿科体内测试计划 (Ped-In Vivo-TP) 我们提出神经母细胞瘤
研究计划建立在丰富注释和高度特征化的患者来源异种移植物 (PDX) 和
其他最近开发的这种疾病的小鼠模型 本计划要测试的中心假设是
可以定义神经母细胞瘤特异性致癌驱动因素和最佳免疫治疗靶点
通过基于经过验证和临床可测量的生物标志物合理设计的疗法进行开发。
通过我们对神经母细胞瘤的专注以及我们在前儿科临床前测试中的核心作用
项目和联盟,我们已经建立了一个调查团队和丰富的资源和试剂来
具有独特的优势来实现 Ped-In Vivo-TP 的目标。在这里,我们建议使用大型(和)。
不断增长的)PDX 模型集合,这些模型已使用最现代的基因组进行了充分表征
技术来应对优先考虑大型抗癌药物军备的挑战
开发,以便可以设计早期生物标志物驱动的临床试验,目的是显示
我们提出了三个具体目标:1) 开发和开发抗肿瘤活性。
2) 进行药物临床前试验
针对确定的治疗弱点,以便优先考虑临床药物,以及 3) 开发
设计临床试验所需的临床前数据组合,以及用于患者选择的稳健生物标志物
与其他临床前测试项目合作,我们将寻求确定是否有发现。
我们的项目与其他儿童癌症相关,并在临床上跨疾病组进行合作
因此,该计划将寻求改变高风险神经母细胞瘤的模式。
患者接受治疗的目标是实质性改善结果,无论是在治愈率方面,还是在
通过降低与当前护理标准相关的毒性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Yael P Mosse其他文献
Yael P Mosse的其他文献
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{{ truncateString('Yael P Mosse', 18)}}的其他基金
NCI Pediatric In Vivo Testing Program: Neuroblastoma
NCI 儿科体内测试项目:神经母细胞瘤
- 批准号:
10300212 - 财政年份:2021
- 资助金额:
$ 69.85万 - 项目类别:
NCI Pediatric In Vivo Testing Program: Neuroblastoma
NCI 儿科体内测试项目:神经母细胞瘤
- 批准号:
10653064 - 财政年份:2021
- 资助金额:
$ 69.85万 - 项目类别:
Proj 1 - Targeting Evolving Therapy Resistance
项目 1 - 针对不断变化的治疗耐药性
- 批准号:
10017934 - 财政年份:2017
- 资助金额:
$ 69.85万 - 项目类别:
Proj 1 - Targeting Evolving Therapy Resistance
项目 1 - 针对不断变化的治疗耐药性
- 批准号:
10265472 - 财政年份:2017
- 资助金额:
$ 69.85万 - 项目类别:
Targeting Oncogenic ALK Signaling in Neuroblastoma
靶向神经母细胞瘤中的致癌 ALK 信号转导
- 批准号:
7694503 - 财政年份:2009
- 资助金额:
$ 69.85万 - 项目类别:
Targeting Oncogenic ALK Signaling in Neuroblastoma
靶向神经母细胞瘤中的致癌 ALK 信号转导
- 批准号:
8074065 - 财政年份:2009
- 资助金额:
$ 69.85万 - 项目类别:
Targeting Oncogenic ALK Signaling in Neuroblastoma
靶向神经母细胞瘤中的致癌 ALK 信号转导
- 批准号:
9271153 - 财政年份:2009
- 资助金额:
$ 69.85万 - 项目类别:
Targeting Oncogenic ALK Signaling in Neuroblastoma
靶向神经母细胞瘤中的致癌 ALK 信号转导
- 批准号:
10198851 - 财政年份:2009
- 资助金额:
$ 69.85万 - 项目类别:
Targeting Oncogenic ALK Signaling in Neuroblastoma
靶向神经母细胞瘤中的致癌 ALK 信号转导
- 批准号:
8462569 - 财政年份:2009
- 资助金额:
$ 69.85万 - 项目类别:
Targeting Oncogenic ALK Signaling in Neuroblastoma
靶向神经母细胞瘤中的致癌 ALK 信号转导
- 批准号:
10626812 - 财政年份:2009
- 资助金额:
$ 69.85万 - 项目类别:
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相似海外基金
NCI Pediatric In Vivo Testing Program: Neuroblastoma
NCI 儿科体内测试项目:神经母细胞瘤
- 批准号:
10300212 - 财政年份:2021
- 资助金额:
$ 69.85万 - 项目类别:
NCI Pediatric In Vivo Testing Program: Neuroblastoma
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- 批准号:
10653064 - 财政年份:2021
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