New Tools for Prostate Cancer Detection and Prognostication

描述（由申请人提供）：斯坦福大学的金丝雀癌症早期检测中心促进基于有效的早期癌症检测和管理需要血液和分子成像测试相结合的假设的研究计划。该中心汇集了在体外和体内诊断领域工作的医生和科学家，以推进癌症患者的护理，最初的重点是肺癌，卵巢癌，胰腺癌和前列腺癌。PSA检测目前是前列腺癌筛查和管理的基石。然而，由于PSA具有不完美的灵敏度和特异性，前列腺癌经常被诊断不足和过度诊断，导致癌症和不必要的活检被遗漏。需要更好的方法来准确检测前列腺癌，并确定其进展的能力。该提案利用了斯坦福大学医学和工程学院、斯坦福大学癌症中心、金丝雀基金会和国家癌症研究所的优势，包括癌症纳米技术卓越中心（CCNE）U54和体内细胞和分子成像中心（ICMIC）P50。我们还与弗雷德哈钦森癌症中心的教师建立了重要的联系。在本提案中，我们概述了两种不同且互补的策略，将尖端技术应用于前列腺癌检测和管理的双重方法。在项目#1中，我们提出了我们新开发的磁纳米传感器的适应性，以用于前列腺癌检测和诊断的血液生物标志物的多重分析。该平台的灵敏度是ELISA检测的1000倍，具有64倍的多重检测能力，并跨越60年的动态范围，能够对设计用于高灵敏度和特异性的复杂生物标志物组进行询问。在项目#2中，我们建议采用我们最新的超声技术，使用肿瘤血管生成靶向微泡来成像前列腺癌。微泡是由脂质外壳包裹的气泡，脂质外壳用靶向肿瘤相关血管生成的抗体功能化。当在成像前引入血流中时，VEGFR2靶向微泡与肿瘤新生血管的内皮细胞结合，以在超声期间提供增强的对比度。结合TRUS（经直肠超声），这种方法将提高筛查过程中检测的准确性。我们的长期目标是联合收割机结合我们的血液生物标志物和成像方法，以准确早期检测和诊断前列腺癌。

DESCRIPTION (provided by applicant): The Canary Center for Cancer Early Detection at Stanford fosters research programs based on the hypothesis that effective early cancer detection and management will require a combination of blood and molecular imaging tests. The center is bringing together physicians and scientists that work in the areas of in vitro and in vivo diagnostics to advance cancer patient care with an initial focus on lung, ovarian, pancreatic and prostate cancers. PSA testing currently serves as the cornerstone for prostate cancer screening and management. However, because PSA suffers from imperfect sensitivity and specificity, prostate cancer is frequently under- and over- diagnosed, resulting in missed cancers and unnecessary biopsies. Better methods are needed to accurately detect prostate cancer, and to determine its capacity for progression. This proposal leverages strengths at the Schools of Medicine and Engineering at Stanford University, the Stanford Cancer Center, the Canary Foundation, and the National Cancer Institute, including a center for cancer nanotechnology excellence (CCNE) U54 and an in vivo cellular and molecular imaging center (ICMIC) P50. We also form important links to faculty at the Fred Hutchinson Cancer Center. In this proposal we outline two distinct and complementary strategies for applying cutting edge technologies to the dual approach for the detection and management of prostate cancer. In Project #1 we propose the adaptation of our newly-developed magneto-nanosensor to the multiplex analysis of blood-based biomarkers for prostate cancer detection and prognostication. This platform is 1000-fold more sensitive than an ELISA assay, has 64-multiplex capacity, and spans a dynamic range of 6 decades, enabling the interrogation of complex biomarker panels designed for high sensitivity and specificity. In project #2 we propose the adaptation of our latest ultrasound technology using tumor angiogenesis-targeted microbubbles to image prostate cancer. Microbubbles are gaseous bubbles encased by lipid shells functionalized with antibodies that target tumor-associated angiogenesis. When introduced into the bloodstream before imaging, VEGFR2-targeted microbubbles bind to the endothelial cells of the tumor neovasculature to provide enhanced contrast during ultrasound. Incorporated into TRUS (transrectal ultrasound), this approach will increase the accuracy of detection during the screening process. Our long-term goal is to combine our blood-based biomarker and imaging approaches to the accurate early detection and prognostication of prostate cancer.