PDX Core

摘要 PDX Core的目标是提供高质量、临床相关和分子注释的PDX模型 对于德克萨斯大学PDX开发和试验中心(UTPDTC)中描述的研究项目 通过利用我们机构的PDX资源并使用严格的 质量标准，使模型可以用来指导临床试验开发。因为U54基金 限制并使事情尽可能简单，这款U54 PDX核心只能在MD Anderson上运行 癌症中心有足够多的手术标本来满足这笔赠款的需要。这个 已有的UTSWPDX肺癌模型(~40)通过肺癌的NCI孢子建立 (P50CA70907)将由UTSW在项目1中使用，新的和现有的UTMDACC PDX型号将由 MDACC的PDX核心将提供给各种项目，包括项目1的UTSW组件。 根据这项UTPDTC赠款开发和/或表征的PDX模型将适用于其他癌症 研究人员通过NCI患者衍生模型存储库和PDX开发和试验中心 研究网络(PDXNet)。我们处于独特的地位，可以为研究提供高质量的PDX模型 在这项拨款申请中描述的，并为癌症研究社区。我们的研究团队已经建立了 人肺癌、乳腺癌、结直肠癌和胰腺癌的506个PDX模型和完整的外显子组 分别对176个和94个模型进行测序和RNA测序。我们目前正在参与 NCI通过两个独立的NCI补充奖在PDX模型上的合作倡议。我们将使用 NCI制定了严格的质量标准，以生成和表征PDX模型，并提供高 用于临床前研究的高质量PDX模型。此外，我们将加强PDX模式的多样性，以 通过利用世界一流的翻译专业知识和访问权限回答临床和/或翻译问题 用于生成新的PDX模型的机构所特有的人体组织。例如，两万多人 UTMDACC每年进行外科手术和50,000次诊断和/或治疗。 我们的患者同意书已经经过NCI工作人员的审查，适合与 癌症研究社区通过NCI的患者衍生模型存储库和PDXNet。为了实现我们的目标 以支持UTPDTC项目和PDXNet活动为目标，我们将提供高质量的临床和 在对已建立的PDX模型进行严格的质量测试后，分子注释的PDX并增强了多样性 通过生成和表征新模型来管理PDX模型。这项拟议的研究具有重大的公共卫生意义 因为为本文所述的临床前研究提供最高质量的PDX模型 并应用于癌症研究界，最终将完善和加快新技术的发展 有效的生物标记物驱动的癌症治疗，帮助癌症患者与他们的疾病作斗争。

Abstract The goal of the PDX Core is to provide high-quality, clinically relevant, and molecularly annotated PDX models for the research projects described in the University of Texas PDX Development and Trial Center (UTPDTC) grant application by leveraging PDX resources at our institutions and developing new PDX models using rigorous quality standards so that the models can be used to guide clinical trial development. Because of U54 funding limitations and to keep things as simple as possible, this U54 PDX Core will only function at the MD Anderson Cancer Center which has more than enough surgical specimens coming in to fulfill the needs of this grant. The existing UTSW PDX lung cancer models (~40) developed through the NCI SPORE in Lung Cancer (P50CA70907) will be used by UTSW in Project 1, and new and existing UTMDACC PDX models created by the PDX Core at MDACC will be supplied to the various projects including for the UTSW component of Project 1. The PDX models developed and/or characterized under this UTPDTC grant will be available to other cancer researchers through the NCI Patient-Derived Models Repository and PDX Development and Trial Centers Research Network (PDXNet). We are in a unique position to provide high-quality PDX models for studies described in this grant application and for the cancer research community. Our research team has established 506 PDX models from human lung, breast, colorectal, and pancreatic cancers and completed whole exome sequencing and RNA sequencing for 176 and 94 of these models respectively. We are currently participating in the NCI's collaborative initiative on PDX models through two separate NCI supplemental awards. We will use the rigorous quality standards developed by the NCI to generate and characterize PDX models and provide high- quality PDX models for preclinical investigations. Furthermore, we will enhance the diversity of PDX models for answering clinical and/or translational questions by leveraging the world-class translational expertise and access to human tissues unique to our institutions for generating new PDX models. For example, more than 20,000 surgical procedures and 50,000 diagnostic and/or treatment procedures are performed annually at UTMDACC. Our patient consent forms have already been reviewed by NCI staff and are appropriate for sharing PDXs with the cancer research community through NCI's Patient-Derived Models Repository and PDXNet. To achieve our goal of supporting the UTPDTC projects and PDXNet activities, we will provide high-quality clinically and molecularly annotated PDXs after rigorous quality testing of established PDX models and enhance the diversity of PDX models by generating and characterizing new models. The proposed study has significant public health implications because providing the highest quality PDX models for the preclinical investigations described in this application and to the cancer research community will ultimately improve and accelerate the development of new effective biomarker-driven cancer therapies, helping cancer patients fight their disease.