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。早期