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

项目总结/摘要 俄勒冈州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 在过去十年中，开发了体外药物分析，以指导癌症药物分配的合理决策 患者，从而改善患者的治疗效果并降低医疗成本。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，在离体药物的几乎所有方面都有显着改善， 试验.我们的工作迄今已导致许多同情使用的情况下，以及新的调查员启动 临床试验认识到临床友好的离体药物敏感性平台的广泛实用性，我们建立了一个 商业实体，SEngine Precision Medicine，其使命是提供患者衍生的功能测试 用于研究、临床研究和药物开发的肿瘤细胞。在这里，我们寻求超越概念证明 在癌症研究中心、社区医院和个人用户更广泛采用的测定中。我们 将在“N of 1”设置和前瞻性观察中对检测试剂盒的预测性能进行基准测试 研究，并使用此基线性能来推动方法的开发，以进一步提高其预测性 值我们将继续优化药物选择，将体外药物检测与患者特异性基因组检测相结合， 分析和临床数据。同时，我们将根据需求分析开发一个报告系统， 潜在的最终用户，如临床医生和学术研究中心。OHSU将提供精确的专业知识 AML药物，原代白血病细胞的功能测试和临床试验，并将协助分析 优化. FHCRC将提供实体瘤细胞功能检测的专业知识，首先关注 乳腺癌、癌症基因组学和临床试验;并将协助分析优化和基准测试。 SEngine将开发CLIA认证的检测方法，优化样品分析工作流程，并开发报告系统 为最终用户。所有三个研究中心将共同合作，以证明检测试剂盒的机构间熟练程度。在 至少有五个额外的学术中心已同意为该项目提供患者来源的肿瘤细胞， 预计这一数字将在赠款期间增加。合作机构还将提供 我们的绩效和报告系统的重要反馈。我们这个项目的最终目标是制作一个 基于离体药物筛选的精细功能基因组平台，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.