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早期妇科癌症。 通过筛查（尤其是高危人群）进行筛查是一种有吸引力的策略，可以及时发现 干预但常规努力并未改善细胞外囊泡（EV；30-200）。 直径纳米）被细胞主动释放到循环中，携带不同的分子货物。 捕获这些信息可以提供一个实时窗口来监测肿瘤负荷和动态 分子变化和潜在的 OvCa 前体病变我们的目标是推进我们的转化 EV。 用于早期 OvCa 诊断的检测，重点关注其最致命的亚型，高级别浆液性卵巢 我们与癌症（HGSOC）建立了强大的战略学术-工业联盟。 马萨诸塞州总医院、布莱根妇女医院和外泌体诊断与 我们将实施自动化和技术改进两个主要目标。 高通量平台 OCEANA（使用纳米等离子体阵列进行卵巢癌外泌体分析）。 我们还将构建 EV 标记组，以增强 EV 扩展检测的诊断能力。 我们将使用源自患者的生物标志物严格评估 OCEANA 和 EV 生物标志物。 跨临床范围（例如良性、早期、晚期）的类器官和样本 我们有四个具体目标来实现这些目标。 目标 1. 我们将开发一种基于磁盘的盒式磁带，用于快速、自动化的全面 EV 隔离。 基础技术将是我们的双模式色谱 (DMC)，该技术已证明 目标 2：我们将为血浆建立一个扩展的 EV 标记组。 HGSOC 检测由患者来源的类器官和 EV 提供信息，特别是 EV 蛋白和 mRNA。 结果将被合并以形成多分析物标记组。目标 3。我们将分析来自小鼠的 EV。 托管 HGSOC 患者来源的异种移植物以研究肿瘤进展与 目标 4. 我们将筛查患有良性或恶性卵巢的女性的循环 EV。 该项目将严格评估 OCEANA 的临床表现。 OCEANA 作为全面 EV 分析的变革性工具，临床研究也将得到验证。 最终，我们设想 EV 作为早期检测 HGSOC 的有效循环生物标志物。 将该技术转化为跨研究和临床环境的癌症护理监测工具。