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)将加速对最常见类型的肺癌的准确诊断的进展， 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（CTC）、循环肿瘤微栓子（CTM），和 CTC衍生的核酸特征。拟议的纳米技术平台战略性地吸引了来自 材料科学和电气工程（项目负责人王山博士），微流体等多个领域 （合作研究者Stephen Quake博士和Utkan德米尔奇博士）、临床肿瘤学（项目临床医生石楠博士 Wakelee和Viswam Nair）、商业（重要贡献者，Luis Carbonell先生，MBA）和生物信息学 和统计数据（合作者和顾问Olivier Gevaert博士和Jarrett Rosenberg博士）共同创建快速， 为NSCLC患者提供准确、可靠的诊断工具。我们奋进于创造或开发纳米技术 从用于癌症和肿瘤细胞富集的基于血液的蛋白质组学的磁纳米传感器， 使用磁筛选和磁悬浮细胞分选的磁分离，以分子表征 使用靶向多重基因表达和下一代CTC和CTM测序， 细胞水平。我们的平台不仅专注于诊断癌症，还专注于确定癌症的进程和速度。 癌症进展和治疗下的演变。在最初的两年里，我们将制定拟议的 纳米技术-磁性纳米传感器、磁性分离装置、单细胞基因表达测定 和基因测序，以纳入假定的癌症生物标志物-然后在两个队列中测试它们。 NSCLC患者：早期诊断，晚期选择治疗， 监测.我们可以从斯坦福大学医院提供的患者中获得大量的临床样本 和MD安德森癌症中心。这些设备不会单独测试，而是与 来自CT（计算机断层扫描）和PET（正电子发射）的患者临床和成像数据 断层扫描）-CT，这是目前诊断和监测肺部疾病的护理标准的重要组成部分 癌我们预计，新的纳米技术和相关方法的发展，适用于 选定的血液传播的核酸、蛋白质组学和细胞生物标志物将能够检测早期 NSCLC。对晚期NSCLC患者靶向治疗选择和监测的前所未有的见解 将被记录，以更有效地管理病人比今天的护理标准。这些 纳米技术将使血液生物标志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.