Expanding early cancer detection with high throughput OCEANA - Ovarian Cancer Exosome Analysis with Nanoplasmonic Array

利用高通量 OCEANA 扩大早期癌症检测 - 使用纳米等离子体阵列进行卵巢癌外泌体分析

• 批准号: 10762488
• 负责人: Cesar M Castro
• 金额: $ 87.76万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10762488
• 关键词: Acceleration; Address; Adoption; Ascites; Automation; Benign; Biological Assay; Biological Markers; Blood; Blood Tests; Blood specimen; CA-125 Antigen; Cancer Model; Cancer Patient; Cells; Chromatography; Circulation; Clinical; Clinical Research; Complement; Diagnostic; Diameter; Disease; Early Diagnosis; Epithelial ovarian cancer; Excision; General Hospitals; Genetic Risk; Germ-Line Mutation; Goals; Gynecologic; Hospitals; Image; Industry; Intervention; Lesion; Liquid substance; Malignant - descriptor; Malignant Female Reproductive System Neoplasm; Malignant neoplasm of ovary; Massachusetts; Messenger RNA; Methods; Molecular; Molecular Analysis; Monitor; Mus; Nanotechnology; Nucleic Acids; Operative Surgical Procedures; Organoids; Ovarian; Pathogenesis; Pathology; Patients; Performance; Perinatal; Plasma; Proteins; Quality Control; Research; Resources; Sampling; Screening for Ovarian Cancer; Screening for cancer; Serous; Site; Standardization; Statistical Data Interpretation; System; Systems Biology; Technology; Testing; Thinking; Time; Translating; Tumor Burden; United States; Update; Validation; Woman; advanced disease; assay development; biobank; biomarker panel; cancer biomarkers; cancer care; cancer diagnosis; cancer imaging; cancer subtypes; circulating biomarkers; clinical translation; cohort; comparative; design; diagnostic value; early detection biomarkers; exosome; extracellular vesicles; high risk; high risk population; insight; instrument; liquid biopsy; minimal risk; minimally invasive; molecular dynamics; multidisciplinary; nanoplasmonic; novel; patient derived xenograft model; peripheral blood; prophylactic; prospective; protein biomarkers; protein profiling; screening; success; tool; tumor progression; tumorigenesis

Ovarian cancer (OvCa) remains the most lethal gynecologic cancer in the United States. Early detection through screening, particularly of high-risk populations, is an appealing strategy for timely intervention yet conventional efforts have not improved survival. Extracellular vesicles (EVs; 30-200 nm in diameter) are actively released by cells into circulation, carrying diverse molecular cargo. Capturing this information could provide a real-time window to monitor tumor burden and dynamic molecular changes and potentially OvCa precursor lesions. We aim to advance our translational EV assay for early OvCa diagnosis with a focus on its most lethal subtype, high-grade serous ovarian cancer (HGSOC). We formed a powerful strategic academic-industry alliance between Massachusetts General Hospital, Brigham and Women's Hospital, and Exosome Diagnostics and have laid out two primary objectives. Technology refinement. We will implement an automated and high-throughput platform, OCEANA (Ovarian Cancer Exosomal Analysis with Nanoplasmonic Array). We will also construct an EV marker panel to enhance the diagnostic power of EV assays. Expanded clinical validation. We will rigorously evaluate OCEANA and EV biomarkers using patient-derived organoids and samples across the clinical spectrum (e.g., benign, early, advanced stages) from a world-class and gynecologic-focused biorepository. We have four Specific Aims to achieve these objectives. Aim 1. We will develop a disk-based cartridge for fast, automated total EV isolation. The underlying technology will be our dual-mode chromatography (DMC) which has demonstrated superior EV extraction from plasma. Aim 2. We will establish an expanded EV-marker panel for HGSOC detection informed by patient-derived organoids and EVs. Specifically, EV protein and mRNA results will be combined to make a multi-analyte marker panel. Aim 3. We will analyze EVs from mice hosting HGSOC patient-derived xenografts to study the relationship between tumor progression and circulating EVs. Aim 4. We will screen circulating EVs in women with benign or malignant ovarian conditions, rigorously evaluating OCEANA's clinical performance. Impact. This project will establish OCEANA as a transformative tool for comprehensive EV analyses. The clinical study will also validate EVs as a potent circulating biomarker for early detection of HGSOC. Ultimately, we envision translating the technology as a monitoring tool for cancer care across research and clinical settings.

卵巢癌(OvCa)仍然是美国最致命的妇科癌症。早些时候 通过筛查进行检测，特别是对高危人群进行筛查，是及时进行检测的一项有吸引力的战略。 干预然而，常规的努力并没有提高存活率。细胞外小泡(EVS；30-200 NM)被细胞主动释放到循环中，携带着不同的分子货物。 捕获这些信息可以提供一个实时窗口来监控肿瘤负荷和动态 分子变化和潜在的OvCa前驱病变。我们的目标是推进我们的翻译电动汽车 以高级别浆液性卵巢亚型为重点的OvCa早期诊断方法 癌症(HGSOC)。我们形成了一个强大的战略学术-产业联盟， 马萨诸塞州总医院、布里格姆妇女医院和Exosome诊断和 列出了两个主要目标。技术改造。我们将实施自动化和 高通量平台，SOINA(利用纳米浆阵列进行卵巢癌外切体分析)。 我们还将建造EV标记板，以提高EV检测的诊断能力。已扩展 临床验证。我们将使用患者来源的生物标志物严格评估Ocean和EV生物标志物 临床范围内(如良性、早期、晚期)的有机物和样本 世界一流的、专注于妇科的生物仓库。我们有四个具体的fic目标来实现这些目标。 目标。目标1.我们将开发一种基于磁盘的盒，用于快速、自动地分离全EV。这个 基础技术将是我们的双模式层析(DMC)，它已经证明 从血浆中提取优越的电动汽车。目标2.我们将建立一个扩大的EV标记物小组 HGSOC检测由患者衍生的有机化合物和EVS提供信息。肠道病毒的特异性fi、蛋白和基因 结果将被组合成一个多分析物标记面板。目标3.我们将分析老鼠身上的电动汽车 宿主HGSOC患者来源的异种移植物研究肿瘤进展与 流通中的电动汽车。目标4：我们将筛查卵巢良性或恶性患者的循环EVS 条件，严格评估Oceana的临床表现。冲击力。该项目将建立 大洋洲作为全面电动汽车分析的变革性工具。这项临床研究也将验证 EVS可作为早期发现HGSOC的有效循环标志物。最终，我们设想 将这项技术转化为跨研究和临床环境的癌症护理监测工具。