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 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PDX开发新的PDX模型， 质量标准，以便模型可用于指导临床试验开发。由于U 54的资助 限制，并保持事情尽可能简单，这U 54 PDX核心将只在MD安德森功能 癌症中心有足够的手术标本来满足这项赠款的需要。的 现有UTSW PDX肺癌模型（约40个）通过NCI SPORE在肺癌中开发 （P50 CA 70907）将由UTSW在项目1中使用， 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 在这个补助金申请和癌症研究社区中描述。我们的研究团队已经建立 来自人肺癌、乳腺癌、结直肠癌和胰腺癌的506个PDX模型和完整的全外显子组 测序和RNA测序分别为176和94这些模型。我们目前正在参与 NCI通过两个独立的NCI补充奖项在PDX模型上的合作计划。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，并提供高质量的 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， 我们的研究机构所独有的人体组织来生成新的PDX模型。例如，超过20，000 UTMDACC每年进行50，000例外科手术和诊断和/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 癌症研究社区通过NCI的患者衍生模型库和PDXNet。实现我们 支持UTPDTC项目和PDXNet活动的目标，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， 通过生成和表征新的模型来优化PDX模型。这项研究对公众健康有重大意义。 影响，因为提供最高质量的PDX模型，用于本研究中描述的临床前研究 应用和癌症研究社区将最终改善和加速新的发展， 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.