A New Approach for the Non-Invasive Detection of Bladder Cancer

膀胱癌无创检测的新方法

• 批准号: 7802474
• 负责人: Christopher Sears
• 金额: $ 18.72万
• 依托单位: AMBERGEN, INC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-28 至 2011-09-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7802474
• 关键词: Area; Biological Assay; Biological Markers; Biotechnology; Boston; Cancer Detection; Cancer Patient; Cell Line; Center for Cancer Research at the Massachusetts Institute of Technology; Characteristics; Clinical; Collaborations; Collection; Core Facility; Country; Cystoscopy; Cytology; DNA; Detection; Development; Diagnostic; Diagnostic Neoplasm Staging; Diagnostic Procedure; Diagnostic tests; Drops; Early Diagnosis; Environment; Evaluation; FGFR3 gene; Genes; Goals; Hospitals; In Vitro; Laboratories; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Mass Spectrum Analysis; Methods; Molecular; Molecular Analysis; Mutate; Mutation; Mutation Detection; Non-Invasive Cancer Detection; Operative Surgical Procedures; Organ; Pathogenesis; Patients; Phase; Population; Procedures; Proteins; Proteomics; Quality of life; Recurrence; Research; Sampling; Scanning; Scientist; Screening procedure; Staging; Surveys; Survival Rate; System; TP53 gene; Testing; Tissues; Tumor stage; Tumor-Associated Process; Urine; Woman; anticancer research; base; high risk; improved; men; mutant; novel strategies; professor; prototype; public health relevance; research study; tool; tumor; urologic

DESCRIPTION (provided by applicant): There is an urgent need to develop an effective method for detection of primary and recurrent bladder cancer. Bladder cancer is the fourth most common malignancy in men and the ninth most common malignancy in women in Western countries. If identified early, bladder cancer is characterized by a high survival rate (94%). However, the survival rate drops significantly, to as low as 14%, if spread to other organs has occurred. Bladder cancer is also characterized by a high recurrence rate, (50% - 90%). Consequently, bladder cancer patients must undergo frequent cystoscopic surveillance. The goal of this project is to explore the feasibility of a noninvasive diagnostic test from urine that would allow early detection of new onset, as well as recurrent, bladder cancers, and which would provide an effective tool for cancer staging. Such a test, if applied to high-risk populations or surveyed patients could significantly increase survival rates, and could contribute to improved life quality and duration. Conventional diagnostic methods that involve cystoscopy and cytology are either invasive (cystoscopy), or are relatively insensitive (cytology). We propose to apply a new method based on mass spectrometry of in vitro expressed proteins (MASSIVE- PRO) that will enable detection of small fractions of mutated DNA present in the urine of bladder cancer patients. AmberGen has performed preliminary experiments that demonstrate feasibility in several key areas of this proposal. In Phase I, the MASSIVE-PRO system will be evaluated for detection of mutations in a panel of relevant genes first using mixtures of cell line DNA samples, and later using clinical samples from bladder cancer patients. The goal will be to detect mutations in Kras/Hras, FGFR3 (which are markers of low staged/low grade tumors) and p53 (which is a marker of high stage/high grade tumors) occurring at the 5% or lower level in the sample. A small set of matched tissues and urines will be provided by Dr. Kevin Loughlin, Professor of Surgery and Director of Urologic Research at Brigham and Women's Hospital (Boston, MA). During phase II, a molecular assay based on the results of Phase I will be further developed and evaluated in a clinical laboratory environment for detection of early bladder cancer. PUBLIC HEALTH RELEVANCE: There is an urgent need to develop an effective method for non-invasive detection of early stage urothelial bladder cancer, which is one of the most common cancers, and has one of the highest recurrence rates. The current standard methods for screening rely either on cytology, which has only 20% sensitivity, or on cystoscopy, which often results in false positives, and is invasive and expensive. The goal of this Phase I project is to explore the ability of a new molecular assay method based on mass spectrometry to detect early stages of urothelial bladder cancer by analyzing DNA obtained from urine for the presence of mutations in key genes associated with bladder cancer pathogenesis.

描述（由申请人提供）：迫切需要开发一种检测原发性和经常性膀胱癌的有效方法。膀胱癌是男性中第四大最常见的恶性肿瘤，也是西方国家女性第九最常见的恶性肿瘤。如果早点确定，膀胱癌的特征是高存活率（94％）。但是，如果发生到其他器官，生存率显着下降至低至14％。膀胱癌还具有高复发率（50％-90％）的特征。因此，膀胱癌患者必须进行频繁的膀胱镜监测。该项目的目的是探索尿液中无创诊断测试的可行性，该测试将允许尽早发现新发作以及经常性的膀胱癌，并为癌症分期提供有效的工具。这样的测试，如果应用于高风险人群或被调查的患者可能会大大提高存活率，并可能有助于改善生活质量和持续时间。涉及膀胱镜检查和细胞学的常规诊断方法是侵入性（膀胱镜检查），或者是相对不敏感的（细胞学）。我们建议采用一种基于体外表达蛋白质（大量）质谱的新方法，该方法将能够检测出膀胱癌患者尿液中存在的突变DNA小部分。 Ambergen进行了初步实验，这些实验证明了该提案的几个关键领域的可行性。在第一阶段，将评估大规模Pro系统，以检测首先使用细胞系DNA样品混合物的相关基因的突变，然后使用膀胱癌患者的临床样品。目的是检测KRAS/HRA，FGFR3（是低级/低级肿瘤的标志）和p53（是高阶段/高级肿瘤的标志）的突变，该突变发生在样品中的5％或较低水平。一小部分匹配的组织和尿液将由Brigham and Hospital（马萨诸塞州波士顿）外科教授兼泌尿科研究主任Kevin Loughlin博士提供。在II期期间，将在临床实验室环境中进一步开发并评估基于阶段I的结果，以检测早期膀胱癌。 公共卫生相关性：迫切需要开发一种有效的方法来非侵入性检测早期尿路上皮膀胱癌，这是最常见的癌症之一，并且是复发率最高的癌症之一。当前的筛查标准方法依赖于仅具有20％敏感性的细胞学，或者是膀胱镜检查，这通常会导致假阳性，并且具有侵入性和昂贵。该阶段I项目的目的是通过分析从尿液中获得的DNA来探索一种基于质谱的新分子测定方法检测尿路上皮膀胱癌的早期阶段的能力。