Development of molecular assays for non-invasive bladder cancer detection

描述（由申请人提供）：膀胱癌（BCa）是全球五大最常见的恶性肿瘤之一。仅在美国，2012年新的BCa病例估计为73,500例，估计死亡人数为14,880人。目前，大多数膀胱肿瘤是非肌肉侵袭性的，可以通过经尿道肿瘤切除术来治疗，然而，超过70%的BCa患者在诊断后的头两年内会复发。这种复发现象使BCa成为世界上最普遍的癌症之一。此外，一旦接受治疗，患者将继续接受常规膀胱镜检查，以发现新的肿瘤发展，因此BCa的医疗费用是一个主要负担。该项目的总体目标是开发能够通过尿液分析实现准确、无创检测BCa的检测方法。该项目的第一阶段将确定候选蛋白质生物标志物的最佳组合，以开发诊断特征分析。利用高通量基因组学和蛋白质组学分析技术，我们获得了一系列分子特征，优于目前任何用于BCa检测的尿液分析方法。第一阶段的具体目标是使用替代技术验证这些特征的组件的诊断准确性。目标是建立该方法的技术和科学价值，该提案的第二阶段将确定将选定的基于蛋白质和基于核酸的分子特征开发成具有临床实用性和商业价值的可靠分析的可行性。该策略将包括以下内容：1)在大量不同病例队列中测试第一阶段定义的蛋白质特征的准确性2)在大量不同病例队列中测试核酸特征的效用。3)衍生试剂，用于商业化ELISA和/或III期开发的即时检测。在II期研究结束时，Nonagen Bioscience将准备将一种或多种检测方法商业化，用于膀胱癌高危患者的临床评估。发展无创、基于尿液的膀胱癌检测和疾病状态评估方法将对患者和医疗保健系统都有巨大的好处。

DESCRIPTION (provided by applicant): Bladder cancer (BCa) is among the five most common malignancies worldwide. In the US alone, new BCa cases for 2012 are estimated at 73,500 with estimated deaths at 14,880. At presentation, the majority of bladder tumors are non-muscle invasive, and can be treated by transurethral resection of the tumor, however, more than 70% of patients with BCa will have a recurrence during the first two years after diagnosis. This recurrence phenomenon makes BCa one of the most prevalent cancers worldwide. Furthermore, once treated, patients are under continued surveillance with routine cystoscopy for detection of new tumor development, so the healthcare costs of BCa are a major burden. The overall goal of this project is to develop assays that can achieve the accurate, non-invasive detection of BCa via urinalysis. Phase I of the project will define optimal combinations of candidate protein biomarkers for the development of a diagnostic signature assay. Using high-throughput genomic and proteomic profiling technologies, we have derived a series of molecular signatures that outperform any currently used urinalysis assay for BCa detection. The specific aim of Phase I is to validate the diagnostic accuracy of components of these signatures using alternative techniques. The goal is to establish the technical and scientific merit of the approach Phase II of the proposal will determine the feasibility of developing selected protein-based and nucleic acid-based molecular signatures into robust assays with clinical utility and commercial value. The strategy will include the following: 1) Test the accuracy of protein signatures defined in Phase I in a large diverse cohort of cases 2) Test the utility of nucleic acid signatures in a large diverse cohort of cases. 3) Derive reagents for inclusion into commercial ELISA and/or point-of-care assays to be developed in Phase III. At the end of the Phase II study, Nonagen Bioscience will be ready to pursue commercialization of one or more assays for the clinical evaluation of at-risk patients for bladder cancer. The development of non- invasive, urine based assays for bladder cancer detection and disease status evaluation will be of tremendous benefit to both patients and the healthcare system.