An Academic-Industry Partnership to Advance Functional Genomics for Personalized Oncology.

项目摘要/摘要 俄勒冈健康与科学大学和弗雷德·哈钦森癌症研究中心已经研究了 在过去的十年里，开发了体外药物图谱，以指导癌症药物分配的基本决策 患者，从而改善患者的预后并降低医疗成本。最近的一些突破， 通过我们的合作伙伴关系开发的许多药物在体外药物的几乎所有方面都有了显著的改进 测试。到目前为止，我们的工作已经导致了许多同情的使用案例，以及新的调查员启动 临床试验。认识到临床友好的体外药物敏感平台的广泛用途，我们建立了一个 商业实体SEngine Precision Medicine，其使命是为患者提供派生的功能测试 用于研究、临床研究和药物开发的肿瘤细胞。在这里，我们试图超越概念的验证 在癌症研究中心、社区医院和个人用户更广泛采用的测试中。我们 将在N of 1设置和前瞻性观察中对该分析的预测性能进行基准测试 研究，并利用这一基线表现来推动方法的发展，以进一步提高其预测性 价值。我们将继续通过将体外药物测试与患者特定基因组相结合来优化药物选择 侧写和临床数据。同时，我们将根据需求分析开发一个报告系统，用于 潜在终端用户，如临床医生和学术研究中心。OHSU将提供精密方面的专业知识 治疗AML的药物、原代白血病细胞的功能测试和临床试验，并将协助化验 优化。FHCRC将提供实体肿瘤细胞功能测试方面的专业知识，首先专注于 在乳腺癌、癌症基因组学和临床试验方面；并将协助分析优化和基准测试。 SEngine将开发CLIA认证的分析，优化样品分析工作流程，并开发报告系统 面向最终用户。所有这三个网站将共同努力，以展示机构间的检测熟练程度。在… 至少另外五个学术中心已经同意为这个项目提供患者来源的肿瘤细胞，我们 预计这一数字在授权期内将会增加。合作机构还将提供 为我们的业绩和报告系统提供必要的反馈。我们这个项目的最终目标是制作一个 基于体外药物筛选的精细化功能基因组平台，用户友好的报告界面，以及 在临床护理决策过程中采用该技术。

PROJECT SUMMARY/ABSTRACT Oregon Health & Science University and the Fred Hutchinson Cancer Research Center have worked over the past decade to develop ex vivo drug profiling to guide a rationale decision-making in assigning drugs to cancer patients, thereby improving patient outcomes and reducing healthcare costs. A number of recent breakthroughs, many developed through our partnership, have dramatically improved on nearly all aspects of ex vivo drug testing. Our work to date has led to numerous compassionate-use cases as well as new investigator initiated clinical trials. Recognizing the broad utility for a clinic-friendly ex vivo drug sensitivity platform, we set up a commercial entity, SEngine Precision Medicine, whose mission is to provide functional testing of patient derived tumor cells for research, clinical studies, and drug development. Here we seek to move beyond proof of concept in the assay toward wider adoption by cancer research centers, community hospitals, and individual users. We will benchmark the assay’s predictive performance in both “N of 1” settings and in prospective observational studies, and use this baseline performance to drive the development of methods to further improve its predictive value. We will continue to optimize drug selection by integrating ex vivo drug testing with patient specific genomic profiling and clinical data. In parallel, we will develop a reporting system, based upon requirements analysis, for potential end users such as clinicians and academic research centers. OHSU will provide expertise in precision medicine for AML, functional testing of primary leukemia cells, and clinical trials and will assist with assay optimization. FHCRC will provide expertise in functional testing of cells derived from solid tumors, focusing first on breast cancer, cancer genomics, and clinical trials; and will assist with assay optimization and benchmarking. SEngine will develop CLIA certified assays, optimize sample analysis workflows, and develop a reporting system for end users. All three sites will work together to demonstrate inter-institutional proficiency of the assays. At least five additional academic centers have agreed to provide patient derived tumor cells for this project and we anticipate this number will increase during the granting period. The partnering institutions will also provide essential feedback for our performance and reporting system. Our end goals for this project are to produce a refined functional genomic platform based on ex vivo drug screens, a user-friendly reporting interface, and adoption of the technology in the clinical care decision-making process.