Integrated exosomes profiling for minimally invasive diagnosis and monitoring of cancer

用于癌症微创诊断和监测的综合外泌体分析

• 批准号: 10307656
• 负责人: ANDREW K. GODWIN
• 金额: $ 19.59万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10307656
• 关键词: Integrated; exosomes; profiling; minimally; invasive

Contact PD/PI: Zeng, Yong PROJECT SUMMARY Ewing Sarcoma (EWS) is the second most common primary bone cancer and a deadly threat to US children and adolescents. Desp ite great efforts over the last few decades, early detection of pediatric EWS is still challenging for standard imaging and cytogenetic modalities and very little improvement in long-term survival of EWS has been achieved. Patients initially presenting without clinically overt metastases at diagnosis have a 5- year overall survival of 70-75%; in contrast, the 5-year overall survival for metastatic EWS is below 30% due to high prevalence of disease recurrence/relapse. The long-term survival is 22% to 24% for patients with limited localized relapse and even lower for distant relapse Tissue biopsy for pathological or cytological diagnosis and monitoring of EWS is extremely invasive and difficult, especially in young children. The lack of reliable blood biomarkers presents a serious obstacle to the treatment and management of EWS, more importantly, recurrent or metastatic EWS. Thus novel diagnostic and prognostic biomarkers are urgently needed to improve clinical outcome of this deadly pediatric cancer. Circulating exosomes are emerging as a new paradigm of “liquid biopsy” for non-invasive cancer diagnosis and monitoring. Exosomes are small membrane vesicles of 30-150 nm in size secreted by most cells. Growing evidence has shown important biological roles and clinical relevance of exosomes. In various cancers, tumor-derived exosomes have been found to be accumulated in human biofluids, such as blood, and enriched with a set of biomolecules from the cells of origin, such as proteins and RNAs, which may constitute a “cancer signature”. However, biology and clinical value of exosomes remain largely unknown, due in part to the challenges in isolation and analysis of such small, dynamic and molecularly diverse vesicles. Very few, if any, exosome studies in EWS have been reported. To address this obvious gap in both analytical technologies and the precision medicine for EWS, we propose to develop and validate the nanotechnology-inspired, integrated microfluidic platforms that offer unprecedented analytical capabilities for measuring protein and mRNA markers in circulating exosomes derived from EWS. These new technologies will be validated to profile circulating exosomes in a unique longitudinal series of blood samples from pediatric EWS patients at initial diagnosis, during therapy and off therapy, aiming to identify exosomal markers that can track therapeutic response and detect early disease recurrence. While designed to specifically target EWS as proof-of-principle, this project will ultimately provide transformative platform technologies for basic and clinical investigation of a wide range of malignancies and diseases. . Project Summary/Abstract Page 7

联系PD/PI：Zeng，Yong 项目摘要 尤因肉瘤（EWS）是第二个最常见的原发性骨癌，对我们儿童的致命威胁 和青少年。 DESP 在过去的几十年中，迭代的巨大努力，小儿EWS的早期发现仍在 对标准成像和细胞遗传学方式的挑战，长期生存的改善很少 已经实现了EWS。 患者最初 诊断时没有临床明显转移的没有临床明显转移的表现为5- 年整体生存 70-75％；相反， 5年的总生存期 由于转移性EWS的30％以下 疾病复发/复发的高患病率。 有限的患者的长期生存率为22％至24％ 用于病理或细胞学诊断的遥远继电器组织活检的局部继电器，甚至较低 对EWS的监测极具侵入性和困难，尤其是在幼儿中。缺乏可靠的 更重要的是，血液生物标志物对EWS的治疗和管理构成了严重的障碍 经常性或转移性EWS。迫切需要那种新颖的诊断和预后生物标志物 改善这种致命的小儿癌的临床结果。循环外泌体正在作为新的 用于非侵入性癌症诊断和监测的“液体活检”范式。外泌体是小膜 大多数细胞分泌的囊泡大小为30-150 nm。越来越多的证据表明了重要的生物学作用 外泌体的临床相关性。在各种癌症中，发现肿瘤衍生的外泌体是 积累在人类生物群中，例如血液，并富含来自细胞的一组生物分子 起源，例如蛋白质和RNA，可能构成“癌症”。但是，生物学和临床 外泌体的价值在很大程度上是未知的，部分原因是隔离和分析了这种挑战 小，动态和分子多样的蔬菜。在EWS中很少（如果有的话）研究 报告。为了解决分析技术和EWS的精确医学中的这一明显差距，我们 开发和验证纳米技术风格的，集成的微流体平台的建议 在循环外泌体中测量蛋白质和mRNA标记的前所未有的分析能力 源自EWS。这些新技术将经过验证以在独特的 初始诊断，治疗期间和关闭的小儿EWS患者的纵向血液样本 治疗，旨在识别可以跟踪治疗反应并检测早期疾病的外泌体标记 复发。虽然旨在将EWS专门定为原理证明，但该项目最终将提供 用于广泛恶性和临床研究的变革性平台技术 疾病。 。 项目摘要/摘要页面7