Non Invasive Treatment Response Monitoring and molecular characterization of NSCLC using Cell-free DNA isolated by an AC Electrokinetic Device

描述(由申请人提供)：我们的总体目标是将一种具有成本效益的、快速的、治疗点治疗反应监测系统商业化，该系统可以识别非小细胞肺癌(NSCLC)的无反应患者，这对决定治疗过程的医生至关重要。在这个第一阶段的提案中，我们将展示一种廉价的交流电动(ACE)芯片原型，该芯片可以有效地直接从血浆中快速分离无细胞循环DNA，并为将CFC DNA定量作为治疗反应监测(TRM)的分子标记奠定了概念证明。肺癌是人类最常见的成人癌症，发病率和死亡率都很高。2008年，全球新增肺癌病例161万例，死亡138万例。预后通常很差：在所有肺癌患者中，只有15%的人在确诊后存活了五年。监测治疗反应的标准方法是每2-3个月进行一次系列成像。在研究环境中，RECIST标准被用来定义进展，但在常规实践环境中，几乎任何肿瘤大小的增加都可以被称为进展并引发治疗的改变。因此，在影像上发现进展的时候，肿瘤已经进展了2-3个月，而治疗医生并不知情。更频繁的成像增加了临床护理的成本，并使患者暴露在不必要的辐射中。血浆和血清中的游离DNA已被发现是肺癌治疗后立即评估治疗反应的一个很好的标志物，因此可以用来更快地改变治疗以改善结果。交流电动(ACE)分离和定量无细胞循环DNA(CFCDNA)是一种在不增加成本的情况下进行治疗反应监测的有吸引力的方法。该项目将专注于使用专有的ACE设备从非小细胞肺癌患者血液中分离和分析氟氯化碳DNA的方面。第一阶段提案的具体目标是：1--确定ACE结果的日常可变性。2-在一项小型人体研究中，使用血液样本数据确定肿瘤大小变化的放射学估计与ACE估计之间的关系。未来的第二阶段提案将构建一个商业化的分析系统，进行一项100名患者的研究，其中将使用ACE技术确定无应答者，然后切换治疗过程，为患者提供更有利的结果。第二阶段的研究还将开发一种POC检测方法，供FDA提交。

DESCRIPTION (provided by applicant): Our overall goal is to commercialize a cost effective, rapid, point-of-care, treatment response monitoring system that can identify non-responding patients with non-small cell lung cancer (NSCLC) that would be vital to doctors who determine the course of therapy. In this Phase I proposal, we will demonstrate that an inexpensive prototype AC electrokinetic (ACE) Chip developed at Biological Dynamics, Inc. can effectively isolate cell-free circulating DNA directly from plasma rapidly, and establish the proof of concept for using CFC DNA quantitation as a molecular signature for treatment response monitoring (TRM). Lung Cancer is the most common human adult cancer in terms of both incidence and mortality. In 2008, there were 1.61 million new cases, and 1.38 million deaths due to lung cancer worldwide. Prognosis is generally very poor: of all people with lung cancer, only 15% survive for five years after diagnosis. The standard method of monitoring of response to therapy is serial imaging done every 2-3 months. In the research setting, RECIST criteria are used to define progression, but in the regular practice setting, nearly any increase in tumor size can be called progression and initiate change in therapy. Therefore, by the time progression is identified on the imaging, the tumor has been progressing for the previous 2-3 months without knowledge of treating physician. More frequent imaging raises the cost of clinical care and exposes patient to unnecessary radiation. Cell-free DNA in both plasma and serum has been found to be a good marker in lung cancer to evaluate response to therapy immediately after therapy is initiated, and therefore could be used to cause a more immediate change in therapy to improve outcomes. AC Electrokinetic (ACE) isolation and quantification of cell-free circulating DNA (CFC DNA) represents an attractive way to perform treatment response monitoring without increasing the cost. This project will focus on the aspect of using a proprietary ACE device to isolate and analyze CFC DNA from NSCLC patient blood. The specific aims for the Phase I proposal are: 1 - Determine day-to-day variability of ACE results. 2 - In a small human study, determine relationship between radiological estimate of change in tumor size and ACE estimate using blood sample data. A future Phase II proposal will construct an analytical system for commercialization, perform a 100 patient study where non-responders will be identified using the ACE technology and then switch the course of treatment to provide more favorable outcomes to the patient. The Phase II study will also develop a POC assay for FDA submission.