PDX Core

摘要 PDX Core 的目标是提供高质量、临床相关且分子注释的 PDX 模型 用于德克萨斯大学 PDX 开发和试验中心 (UTPDTC) 描述的研究项目 通过利用我们机构的 PDX 资源并使用严格的方法开发新的 PDX 模型来资助申请 质量标准，以便模型可用于指导临床试验开发。由于U54资助 限制并让事情尽可能简单，此 U54 PDX 核心仅在 MD 安德森中心起作用 癌症中心拥有足够多的手术标本来满足这笔拨款的需求。的 现有的 UTSW PDX 肺癌模型（~40）是通过 NCI SPORE 开发的肺癌模型 (P50CA70907) 将由 UTSW 在项目 1 中使用，并且由 UTMDACC 创建的新的和现有的 PDX 模型 MDACC 的 PDX 核心将提供给各个项目，包括项目 1 的 UTSW 部分。 在 UTPDTC 资助下开发和/或表征的 PDX 模型将可用于其他癌症 研究人员通过 NCI 患者衍生模型存储库以及 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 在本拨款申请中以及癌症研究界中进行了描述。我们的研究团队已经建立 506 个来自人类肺癌、乳腺癌、结直肠癌和胰腺癌的 PDX 模型以及完整的全外显子组 分别对其中 176 个和 94 个模型进行了测序和 RNA 测序。我们目前正在参与 NCI 通过两个单独的 NCI 补充奖项在 PDX 模型上开展合作倡议。我们将使用 NCI 制定的严格质量标准，用于生成和表征 PDX 模型并提供高 用于临床前研究的高质量 PDX 模型。此外，我们将增强 PDX 模型的多样性 通过利用世界一流的翻译专业知识和访问来回答临床和/或翻译问题 我们机构特有的人体组织用于生成新的 PDX 模型。例如，超过20,000 UTMDACC 每年进行外科手术以及 50,000 例诊断和/或治疗手术。 我们的患者同意书已经过 NCI 工作人员的审查，适合与以下人员共享 PDX： 通过 NCI 的患者衍生模型存储库和 PDXNet 与癌症研究界建立联系。为了实现我们的 为了支持 UTPDTC 项目和 PDXNet 活动的目标，我们将提供高质量的临床和 对已建立的 PDX 模型进行严格的质量测试后进行分子注释的 PDX，并增强多样性 通过生成和表征新模型来改进 PDX 模型。拟议的研究具有重大公共卫生意义 影响，因为为本文中描述的临床前研究提供最高质量的 PDX 模型 应用和癌症研究界将最终改善和加速新疗法的开发 有效的生物标志物驱动的癌症疗法，帮助癌症患者对抗疾病。

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.