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Integrative Functional Profiling of Tumor-Derived Extracellular Vesicles

肿瘤来源的细胞外囊泡的综合功能分析

基本信息

批准号：
10679069
负责人：
Liang Xu
金额：
$ 6.45万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10679069
关键词：
3-Dimensional Acceleration Address Advanced Development Biological Markers Biological Process Biosensing Techniques Biosensor Blinded Blood Breast Cancer Patient Breast Cancer cell line Cell Communication Cell Line Cells Characteristics Classification Clinical Clinical Research Clinical Treatment Development Devices Diagnosis Diagnostic Dimensions Disease Disease model Disease stratification Drug resistance Early Diagnosis Engineering Epithelium Evolution Extracellular Matrix Face Genetic Complementation Test Goals Human In Vitro MMP14 gene Malignant Neoplasms Matrix Metalloproteinases Measures Mediating Mediator Membrane Mesenchymal Metastatic/Recurrent Methods Microfluidic Microchips Microfluidics Modality Molecular Monitor Mus Nanochip Analytical Device Neoplasm Metastasis Patients Performance Phenotype Pilot Projects Plasma Process Prognosis Property Protein Analysis Proteins Recurrent disease Relapse Reporting Research Sampling Signal Transduction Solid Neoplasm Specimen Staging System Technology Testing Therapeutic Training Translating Tumor Burden Tumor Cell Invasion Tumor Promotion Tumor-Derived Validation Vesicle accurate diagnosis biomarker panel cancer diagnosis chemotherapy clinical diagnosis clinical implementation cohort disease diagnosis drug relapse drug testing early detection biomarkers exosome experimental study extracellular vesicles follow-up improved in vivo innovation liquid biopsy lithography machine learning algorithm malignant breast neoplasm microfluidic technology mouse model nanoengineering nanopattern nanovesicle new technology next generation novel optimal treatments patient derived xenograft model patient stratification personalized cancer therapy personalized management precision medicine precision oncology prognostic protein expression prototype response self assembly technology validation tool treatment response treatment strategy tumor tumor growth tumor microenvironment tumor progression validation studies

项目摘要

PROJECT SUMMARY Clinical implementation of Precision Medicine faces major challenges in precision disease stratification and staging, determining optimal treatment, monitoring therapy response, and overcoming drug resistance and relapse. To address these challenges, there is a critical unmet need for better biomarkers and tests that complement current methods for accurate diagnosis, prognosis and monitoring of response to treatments. Liquid biopsy presents an innovative non-invasive modality for precision oncology as it promises to provide a global view of tumor dynamics. Extracellular vesicles (EVs), including exosomes, are emerging as a new paradigm of liquid biopsy for non-invasive cancer diagnosis and monitoring. Exosomes are 40-150 nm membrane vesicles secreted by most cells and have been identified as essential mediators of cell interactions and signaling that promote tumor metastasis, drug resistance, and relapse. Despite the potential clinical impact of these findings, precise biological functions of exosomes, including matrix metalloproteinases (MMPs)-mediated modulation of tumor microenvironments, and their potential clinical value remain yet to be determined. This is due in part to the daunting challenges in isolation and analysis of these nanovesicles with diverse molecular and functional properties. Here we hypothesize that functional phenotypes of circulating exosomes can provide potent biomarkers for detecting early malignancy, monitoring tumor progression and metastasis, and assessing therapy response in breast cancer. To test this hypothesis, we propose the advanced development and validation of a nano-engineered microfluidic biosensing system capable of integrative analysis of both molecular and functional phenotypes of exosomes in one streamlined workflow. The research will be performed by three specific aims: 1) Expand the MINDS strategy to develop an optimal 3D nano-engineered integrative EV molecular and activity profiling (EV-MAP) nanochip platform; 2) Adapt and optimize the EV-MAP technology for monitoring tumor burden and therapy response using mouse models; and 3) Evaluate and validate the EV-MAP technology for potential applications to clinical diagnosis and classification of breast cancer patients. The new technology will confer superior analytical capabilities to substantially accelerate the functional studies of circulating exosomes. Harnessing exosome activities for diagnostic, prognostic or therapeutic benefit presents a paradigm-shifting mechanism for precision medicine. While focused on breast cancer in this project, our research will ultimately create a transformative tool for studies of a wide range of bioactive exosomes in various malignancies to develop reliable non-invasive liquid biopsy of cancer.

项目总结