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; 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。早期的 通过筛查检测，尤其是高风险人群，是及时的策略 干预但常规努力并没有改善生存。细胞外蔬菜（EVS； 30-200 直径为NM）被细胞积极释放到循环中，携带潜水员分子货物。 捕获此信息可以提供一个实时窗口来监视肿瘤伯恩和动态 分子变化和潜在的OVCA前体病变。我们旨在推进我们的翻译电动汽车 早期OVCA诊断的测定，重点是其最致命的亚型，高级浆液卵巢 癌症（HGSOC）。我们在 马萨诸塞州综合医院，杨百翰和妇女医院，外部诊断和 已经布置了两个主要对象。技术修复。我们将实施自动化， 高通量平台，大洋洲（卵巢癌外泌体分析，纳米质阵列）。 我们还将构建一个EV标记面板，以增强电动汽车测定的诊断能力。扩展 临床验证。我们将使用患者衍生的严格评估大洋洲和EV生物标志物 临床光谱的器官和样品（例如，良性，早期，高级阶段） 世界一流和以妇科为中心的生物座席。我们有四个特定的目标来实现这些目标 目标。 AIM 1。我们将开发一个基于磁盘的墨盒，以快速，自动的总电动汽车隔离。这 基础技术将是我们的双模式色谱法（DMC） 从血浆中提取出色的EV。 AIM 2。我们将建立一个扩展的EV-Marker面板 由患者衍生的类器官和电动汽车告知的HGSOC检测。特异性，EV蛋白和mRNA 结果将组合成一个多分析物标记面板。目标3。我们将分析小鼠的电动汽车 托管HGSOC患者衍生的Xenographictics研究肿瘤进展与 循环电动汽车。目标4。我们将在患有良性或恶性卵巢的女性中筛选循环电动汽车 严格评估Oceana的临床表现的条件。影响。这个项目将建立 Oceana是用于全面EV分析的变革性工具。临床研究还将验证 电动汽车是一种潜在的循环生物标志物，用于早期检测HGSOC。最终，我们设想 在研究和临床环境中将技术转化为癌症护理的监测工具。