PDXNet Data Commons and Coordinating Center

项目总结 患者来源的异种移植(PDX)是一个强大的模型系统，用于评估抗癌药物和 了解耐药的分子机制。通过对患者衍生的药物组合进行应用 模型，有可能获得证据，以确定最有希望的组合，以推进到 在确定的癌症患者亚群中进行临床测试。然而，PDX药物反应与 为了实现这一愿景，需要不同PDX收集的分子特征数据。一个关键方面是 对于社区共享和标准化数据集的大规模分析需要管理良好的资源 来自PDX和其他患者派生的模型。杰克逊实验室-七座桥(JAX-SB)PDX数据 公共和协调中心(PDCCC)在过去5年中一直在应对这一挑战，将 数据生成(PDX开发和试验中心/PDTC)和PDX模型共享(NCI‘s)的努力 患者派生模型存储库/PDMR)PDX开发和试验中心研究的组件 将网络(PDXNet)整合为一个具有凝聚力的跨网络整体。使用创新的云计算和生物信息学 方法，我们的PDCCC为PDXNet提供管理和计算基础设施，以支持PDX 方法标准化、模型共享、数据共享、海量数据分析。到目前为止，我们已经建立了 PDXNet门户，目前包含来自334个新的PDXNet型号信息和数据资源 33种癌症类型的模型。我们的PDCCC团队为财团提供了便利和积极的指导 合作项目，导致几个主要出版物和10个癌症治疗评估计划信函 意向。在此，我们建议增强PDXNet门户并改进我们的组织活动，以解决 NCI和PDX社区阐明的需求，包括：更快地将PDX研究转化为临床试验； 精确组织和共享多组学和治疗反应数据；以及开发预测 临床治疗反应。我们的具体目标是：1)为PDXNet提供强大的PDCCC支持 利益相关者通过常规委员会、人员专业知识和项目工具；2)增强PDXNet门户 内容、功能和数据共享；以及3)开发和实施加速PDX的战略 转化为临床试验。通过这些目标，我们将协调PDXNet的活动，以增加 患者衍生癌症模型治疗研究的价值和加快临床试验的产生。

PROJECT SUMMARY Patient-derived xenografts (PDXs) are a powerful model system to assess efficacy of anti-cancer agents and understand molecular mechanisms of drug resistance. By applying agent combinations against patient-derived models, it is possible to obtain evidence to determine the most promising combinations for advancement to clinical testing in defined sub-populations of cancer patients. However, integration of PDX drug response with molecular characterization data across diverse PDX collections is needed to enable this vision. A key aspect is the need for well-managed resources for community sharing and large-scale analysis of standardized datasets from PDXs and other patient-derived models. The Jackson Laboratory-Seven Bridges (JAX-SB) PDX Data Commons and Coordination Center (PDCCC) has addressed this challenge for the last 5 years, uniting the efforts of the data-generating (PDX Development and Trial Centers/PDTCs) and PDX model sharing (NCI’s Patient-Derived Model Repository/PDMR) components of the PDX Development and Trials Centers Research Network (PDXNet) into a cohesive, trans-Network whole. Using innovative cloud computing and bioinformatic approaches, our PDCCC provides administrative and computational infrastructure for PDXNet to enable PDX method standardization, model sharing, data sharing, and massive-scale data analysis. To date, we have built the PDXNet Portal, which currently contains PDXNet model information and data resources from 334 new models across 33 cancer types. Our PDCCC team has both facilitated and actively guided consortium collaborative projects, leading to several major publications and 10 Cancer Therapy Evaluation Program Letters of Intent. Here, we propose to enhance the PDXNet Portal and refine our organizational activities to address needs clarified by the NCI and PDX communities, including: faster translation of PDX studies to clinical trials; precise organization and sharing of multi-omic and treatment response data; and development of predictors of clinical treatment response. Our Specific Aims are: 1) To provide robust PDCCC support for PDXNet stakeholders through regular committees, personnel expertise, and project tools; 2) To enhance PDXNet Portal content, functionality, and data sharing; and 3) To develop and implement strategies that accelerate PDX translation to clinical trials. Through these Aims, we will coordinate the activities of the PDXNet to increase the value of patient-derived cancer model treatment studies and speed the generation of clinical trials.