SBIR grant application to develop and commercialize a urine based medical diagnostic for the detection of bladder cancer recurrence.

SBIR 拨款申请开发和商业化基于尿液的医学诊断，以检测膀胱癌复发。

• 批准号: 9502460
• 负责人: Trevor Levin
• 金额: $ 68.69万
• 依托单位: CONVERGENT GENOMICS, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9502460
• 关键词: Agreement; Alleles; American; Applications Grants; Biological Assay; Bladder; Bladder Neoplasm; Blood; Cancer Patient; Cell Line; Cells; Cessation of life; Clinical; Clinical Research; Communities; Cystoscopy; Cytology; DNA; DNA sequencing; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Enzymes; Evaluation; Event; Excision; Future; Guidelines; Healthcare Systems; Human; Infection; Informatics; Kidney Calculi; Lead; Libraries; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Medical; Medicine; Methods; Molecular; Monitor; Morbidity - disease rate; Mutation; North America; Operative Surgical Procedures; Patient-Focused Outcomes; Patients; Performance; Phase; Physicians; Preparation; Price; Procedures; Process; Process Measure; Production; Proteins; Reaction; Reagent; Recurrence; Recurrent disease; Reproducibility; Research; Residual Tumors; Sampling; Schedule; Secure; Sensitivity and Specificity; Small Business Innovation Research Grant; Source; Specificity; Standardization; Techniques; Testing; Time; Tumor Burden; Tumor Markers; Urethra; Urine; Urologist; Validation; Visual; base; biomarker panel; cancer cell; cancer diagnosis; cancer recurrence; clinical development; commercialization; cost; design; diagnostic assay; follow-up; health care availability; improved; innovation; minimally invasive; mutant; non-compliance; novel; prospective; rural patients; sample collection; screening; standard of care; tool; tumor; tumor DNA; urologic

Bladder cancer is one of the most common forms of cancer in North America. Most often, bladder cancer presents as superficial disease, which is treatable through surgical resection, but is also associated with recurrence rates of up to 70%. Thus, patients must be monitored at regular intervals following resection of the tumor to assess for recurrence. This monitoring is done by cystoscopy, which requires a scope to be inserted into the urethra and into the bladder to visually inspect the bladder wall, and is associated with significant patient discomfort, poor compliance to the recommended screening schedule, and high screening costs as cystoscopy must be performed by a physician. Indeed, the cost of screening and surgical interventions makes bladder cancer the most expensive cancer to treat on a per patient basis. Finally, small masses are likely to be missed by visual inspection, resulting in sub-optimal assessment of recurrence. The bladder cancer community has recognized the problems with cystoscopy as the primary screening technique, resulting in a number of attempts to develop urine based assays to more accurately assess the presence of recurrent disease. These assays have looked for the presence of cancer cells or specific proteins associated with cancer. Unfortunately, most of these tests lack specificity, as they measure processes that may be present in other non-cancer conditions such as infection or kidney stone disease, or lack sensitivity, as they measure events that are present only in a subset of bladder cancer patients, usually high-grade disease. As a result, none of the urine based tests currently available are recommended by the American Urological Association as a primary screening tool. We propose to take advantage of recent technological advances and our understanding of the molecular processes involved in bladder cancer to develop a comprehensive screening panel that assays the urine of patients. This technique is non-invasive, and we estimate that we will be able to detect more 90-95% of all bladder cancer patients, giving us high sensitivity to detect recurrent disease, including patients with low grade disease who are missed by current screening techniques. We have performed preliminary tests on patient samples and accurately detected tumors in greater than 90% of such patients. We have also performed testing in normal controls, and none have tested positive for the presence of cancer. Thus, we believe that the test will also have high specificity. Our current proposal aims to build upon our preliminary data by expanding the panel of biomarkers that we assay for even greater coverage, and to investigate technical enhancements to improve the sensitivity. This approach will lead to the development of a non-invasive screening assay that will have excellent sensitivity and specificity at a lower price point than current screening techniques. Thus, the successful development of our assay will improve patient outcomes while reducing the cost burden on the health care system.

膀胱癌是北美最常见的癌症之一。最常见的是膀胱癌 表现为浅表性疾病，可通过手术切除治疗，但也与 复发率高达70%。因此，在切除肿瘤后，必须定期监测患者。 肿瘤复发评估。这种监测是通过膀胱镜检查完成的，这需要插入一个范围 进入尿道并进入膀胱以目视检查膀胱壁，并且与显著的 患者不适，对推荐的筛查时间表的依从性差，以及高筛查费用， 膀胱镜检查必须由医生进行。事实上，筛查和手术干预的成本使得 膀胱癌是每个病人治疗费用最高的癌症。最后，小质量很可能是 通过目视检查遗漏，导致复发的次优评估。膀胱癌患者 已经认识到膀胱镜检查作为主要筛查技术存在的问题， 试图开发基于尿的测定以更准确地评估复发性疾病的存在。这些 测定法已经寻找癌细胞或与癌症相关的特定蛋白质的存在。不幸的是， 大多数这些测试缺乏特异性，因为它们测量的过程可能存在于其他非癌症 条件，如感染或肾结石疾病，或缺乏敏感性，因为他们测量的事件， 仅存在于膀胱癌患者的一个子集中，通常是高级别疾病。结果，没有一个尿液 目前可用的基于测试是美国泌尿外科协会推荐的主要测试 筛选工具我们建议利用最近的技术进步和我们对 参与膀胱癌的分子过程，以开发一个全面的筛查小组， 患者的尿液。这项技术是非侵入性的，我们估计，我们将能够检测到更多的90-95%， 所有膀胱癌患者中，使我们对检测复发性疾病具有高灵敏度，包括低 目前的筛查技术漏掉的疾病等级。我们已经进行了初步测试， 患者样本，并在超过90%的此类患者中准确检测肿瘤。我们还表演了 在正常对照组中进行检测，没有一个人检测出癌症的存在。因此，我们认为 测试还将具有高特异性。我们目前的建议旨在通过扩大我们的初步数据， 我们检测的生物标志物小组，以获得更大的覆盖范围，并研究技术改进 以提高灵敏度。这种方法将导致一种非侵入性筛查方法的开发， 将以比当前筛查技术更低的价格点具有优异的灵敏度和特异性。因此 我们的检测方法的成功开发将改善患者的预后，同时减少患者的成本负担。 医疗保健系统。