Molecular Detection and Profiling of Circulating Tumor Cells

循环肿瘤细胞的分子检测和分析

• 批准号: 7800765
• 负责人: Jered Brackston Haun
• 金额: $ 4.42万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-05-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7800765
• 关键词: Address; Antineoplastic Agents; Biological Markers; Biological Process; Biological Sciences; Biopsy; Blood; Blood specimen; Caliber; Cancer cell line; Cell Count; Cell Separation; Cells; Clinical; Cytokeratin; Detection; Development; Devices; Diagnostic; Differentiation Antigens; Disease; Disease Progression; Epidermal Growth Factor Receptor; Epithelial; Evaluation; Family; Goals; Grant; Human; Human body; Incidence; Ions; Lasers; Lateral; Leukocytes; Localized Malignant Neoplasm; Magnetic Resonance; Magnetic Resonance Imaging; Magnetism; Malignant Neoplasms; Measurement; Medical; Medicine; Methods; Microfluidics; Molecular; Molecular Analysis; Molecular Target; Monitor; Nanotechnology; Patients; Pattern; Peripheral; Primary Neoplasm; Procedures; Process; Proteins; Reading; Recovery; Research; Resolution; Ribosomal Protein S6; Sampling; Science; Sensitivity and Specificity; Signal Transduction; Silicon; Site; Specimen; Staging; Stream; System; TACSTD2 gene; Techniques; Technology; Temperature; Therapeutic; Time; Tumor Expansion; Whole Blood; Work; base; cancer cell; cancer diagnosis; cancer therapy; drug development; extracellular; molecular phenotype; multidisciplinary; nanoparticle; neoplastic cell; novel; outcome forecast; peripheral blood; prototype; rapid detection; research study; response; sensor; treatment response; treatment strategy; tumor; validation studies

DESCRIPTION (provided by applicant): The long-term goal of the proposed research is to develop a novel sensor device platform that is capable of detecting and molecularly profiling circulating tumor cells (CTCs) in clinical samples. CTCs are rare cancer cells that have escaped from a primary tumor site and entered the blood stream. They have been identified in the peripheral blood of most patients with metastatic disease as well as in patients with localized cancers, but at exceedingly low levels (approximately 1-100 cells per ml of blood). It is our hypothesis that these peripheral cells can be used for molecular analysis, which could non-invasively provide valuable information for use in prognosis evaluation, anticancer-drug development, and ultimately, personalized cancer therapy based on CTCs. To date, the technology required to molecularly characterize these cells is lacking because existing clinical technologies are too insensitive. In prior research, our lab developed a prototype micro- NMR (p-NMR) sensor chip that has been used to detect cancer cells that are specifically tagged with superparamagnetic nanoparticles. This technique has been termed diagnostic magnetic resonance (DMR), In this proposal 1 seek to significantly advance DMR technology so that it may be applied in clinical use for molecular detection and profiling of CTCs. To achieve this goal, DMR detection sensitivity and specificity will be dramatically increased through the following aims: Aim 1. Extensively optimize the procedures used to tag tumor cells with magnetic nanoparticles targeted to intracellular and extracellular molecular biomarkers, and Aim 2. Develop an integrated microfluidics component that isolates CTCs from other cells in the blood based on size and delivers them directly to the p-NMR sensor. This work represents a multidisciplinary effort that calls on components from the fields of nanotechnology, molecular targeting, magnetic resonance imaging/sensing, and microfluidics to develop a novel device platform capable of interrogating clinical CTC samples, which could enable real-time molecular analysis of tumor samples and facilitate rational treatment decisions in an era where molecularly targeted therapies are emerging. The proposed research has broad applications for studying human cancer cells that are obtained from blood samples, Information could thus be obtained non-invasively to evaluate patient prognosis, devise treatment strategies, and monitor therapeutic response.

描述（由申请人提供）：拟议研究的长期目标是开发一种新型传感器设备平台，能够检测和分子分析临床样本中的循环肿瘤细胞（CTC）。 CTC 是从原发肿瘤部位逃逸并进入血流的罕见癌细胞。它们已在大多数转移性疾病患者以及局部癌症患者的外周血中被发现，但水平极低（每毫升血液约 1-100 个细胞）。我们假设这些外周细胞可用于分子分析，从而无创地为预后评估、抗癌药物开发以及最终基于 CTC 的个性化癌症治疗提供有价值的信息。迄今为止，由于现有的临床技术过于不敏感，因此缺乏对这些细胞进行分子表征所需的技术。在之前的研究中，我们的实验室开发了一种原型微核磁共振 (p-NMR) 传感器芯片，该芯片已用于检测用超顺磁性纳米粒子专门标记的癌细胞。该技术被称为诊断磁共振 (DMR)。在本提案中 1 寻求显着推进 DMR 技术，以便将其应用于临床 CTC 的分子检测和分析。为了实现这一目标，DMR 检测的灵敏度和特异性将通过以下目标显着提高：目标 1. 广泛优化用针对细胞内和细胞外分子生物标志物的磁性纳米粒子标记肿瘤细胞的程序，目标 2. 开发集成的微流体根据大小将 CTC 与血液中的其他细胞分离并将其直接传送至 p-NMR 传感器的组件。这项工作代表了一项多学科的努力，呼吁纳米技术、分子靶向、磁共振成像/传感和微流体领域的组件开发一种能够询问临床 CTC 样本的新型设备平台，从而能够对肿瘤进行实时分子分析在分子靶向疗法兴起的时代，样本并促进合理的治疗决策。拟议的研究在研究从血液样本中获得的人类癌细胞方面具有广泛的应用，因此可以非侵入性地获取信息来评估患者预后、制定治疗策略和监测治疗反应。