Multiscale Nanotechnologies for Comprehensive Assessment of Lung Cancer in Blood

项目摘要/摘要：肺癌是美国最致命的癌症。研究项目2 (P2)将加快对最常见的非肺癌类型的准确诊断的进展 小细胞肺癌(NSCLC)，通过开发多尺度纳米技术来询问血液传播 循环蛋白、自身抗体、循环肿瘤细胞(CTCs)、循环肿瘤微栓子(CTM)以及 CTC衍生的核酸特征。拟议的纳米技术平台战略性地从 材料科学和电气工程的不同领域(项目负责人王山博士)，微流体 (共同研究员Stephen Quake博士和Utkan Demirci博士)，临床肿瘤学(项目临床医生Heather博士 Wakelee和Viswam Nair)，商业(重要贡献者，Luis Carbonell，MBA)和生物信息学 和统计数据(合作者和顾问奥利维尔·格瓦尔特博士和贾雷特·罗森博格博士)共同创建快速、 为非小细胞肺癌患者提供准确、可靠的诊断工具。我们致力于创造或发展纳米技术 从用于基于血液的癌症蛋白质组学和肿瘤细胞浓缩的磁纳米传感器 利用磁筛和磁悬浮细胞分选的磁选，以分子表征 使用靶向多路基因表达和下一代测序技术，在单一的 细胞水平。我们的平台不仅专注于癌症的诊断，而且还专注于确定 癌症在治疗中的进展和演变。在首两年内，我们会发展建议的 纳米技术.磁纳米传感器、磁分离装置和单细胞基因表达分析 和基因测序，以纳入假定的癌症生物标记物-然后在两个队列中测试它们 非小细胞肺癌患者：早期诊断，晚期选择治疗， 监控。我们可以获得斯坦福医院提供的大量临床样本 和MD安德森癌症中心。这些设备不会单独测试，而是与 患者的CT(计算机断层扫描)和PET(正电子发射)的临床和影像数据 断层扫描)-CT，这是目前肺部诊断和监测护理标准的关键部分 癌症。我们预计，新型纳米技术和相关方法的发展将应用于 选定的血源性核酸、蛋白质组和细胞生物标记物将使早期检测成为可能 非小细胞肺癌。对晚期非小细胞肺癌患者靶向治疗选择和监测的前所未有的见解 将被记录下来，比今天的护理标准更有效地管理患者。这些 纳米技术将使血液生物标记物分析在临床上得到广泛采用。

Project Summary/Abstract: Lung cancer is the most deadly cancer in the United States. Research Project 2 (P2) will accelerate advances toward the accurate diagnosis of the most common type of lung cancer, non- small cell lung cancer (NSCLC), via development of multi-scale nanotechnologies to interrogate bloodborne circulating proteins, autoantibodies, circulating tumor cells (CTCs), circulating tumor microemboli (CTM), and CTC-derived nucleic acid signatures. The proposed nanotechnology platforms strategically bring experts from diverse fields of materials science and electrical engineering (Project Leader Dr. Shan Wang), microfluidics (Co-Investigators Drs. Stephen Quake and Utkan Demirci), clinical oncology (Project Clinicians Drs. Heather Wakelee and Viswam Nair), business (Significant Contributor, Mr. Luis Carbonell, MBA), and bioinformatics and statistics (Collaborator and Consultant Drs. Olivier Gevaert and Jarrett Rosenberg) together to create rapid, accurate, and robust diagnostic tools for NSCLC patients. We endeavor to create or develop nanotechnologies ranging from magneto-nanosensors for blood-based proteomics of cancer and tumor cell enrichment with magnetic separation using magnetic sifting and magnetic levitation cell sorting, to molecular characterization using targeted multiplexed gene expression and next-generation sequencing for CTCs and CTM at the single- cell level. Our platforms focus not only on diagnosing cancer, but also on pinpointing the course and pace of cancer progression and evolution under treatment. Within the first two years, we will develop the proposed nanotechnologies – magneto-nanosensors, magnetic separation devices, single-cell gene expression assays and gene sequencing to incorporate putative cancer biomarkers – and then test them on two cohorts of NSCLC patients: those in early stage for diagnosis, and those in advanced stages for therapy selection and monitoring. We have access to large cohorts of clinical samples from patients provided by Stanford Hospital and MD Anderson Cancer Center. These devices will not be tested in isolation, but rather integrated with patients’ clinical and imaging data from CT (computed tomography) and PET (Positron Emission Tomography)–CT, which are a crucial part of the current standard of care for diagnosis and surveillance of lung cancer. We anticipate that the development of novel nanotechnologies and pertinent methods as applied to selected bloodborne nucleic acid, proteomic, and cellular biomarkers will enable the detection of early-stage NSCLC. Unprecedented insights into targeted therapy selection and monitoring for late-stage NSCLC patients will be documented to more effectively manage patients than today’s standard of care. These nanotechnologies will enable blood biomarker analyses to be widely adopted in clinics.