NanoCytology to mitigate overdiagnosis of prostate cancer

 描述（由申请人提供）：前列腺癌是美国男性的主要癌症。目前前列腺癌管理的最大限制是，目前基本上不可能准确地确定哪些患者患有进展为转移性疾病并需要治疗的侵袭性癌症，以及哪些患者患有不会造成伤害的非侵袭性惰性癌症。目前可用于预测前列腺癌的技术缺乏临床实用性、高成本和/或缺乏灵敏度。我们提出了一个新的范例，以准确地识别患有积极监测（每1-3年重复活检）的前列腺癌男性中携带侵袭性与非侵袭性疾病的患者。我们建议通过检测前列腺领域致癌作用来实现这一目标，这是一种导致致癌作用的遗传或环境对整个前列腺产生影响的概念。因此，不仅是肿瘤细胞，而且整个前列腺中更大的细胞群体，否则在活检中看起来是正常的-具有侵袭性癌症风险的指纹。在实地致癌过程中，细胞中发生的一些最初的改变是在纳米级水平上的，并且太小而不能被常规显微镜检测到，就像病理学家检查前列腺活检一样。我们已经开发出一种新的光学技术，部分波光谱（PWS）显微镜（或简单地说，纳米细胞学），这是唯一适合检测这些微妙的变化，在现场致癌。我们已经在759名患者的7种癌症（肺癌、结肠癌、前列腺癌、卵巢癌、食管癌、胰腺癌和甲状腺癌）的先前临床试验中验证了纳米细胞学。在最近对患有Gleason 6疾病的前列腺癌患者进行主动监测的研究中（n = 38），我们发现对组织学正常的前列腺上皮进行的PWS纳米细胞学能够成功预测随后的进展者与非进展者。在未来，我们设想纳米细胞学可以耦合到现有的前列腺癌护理。已经接受积极监测的前列腺癌患者将通过PWS纳米细胞学检查他们的活检，这将识别具有侵袭性和非侵袭性肿瘤的患者。为了实现这一目标，作为SBIR快速通道应用程序的一部分，NanoCytomics将首先开发一种全自动，全载玻片，快速PWS纳米细胞学系统，该系统专门优化以获取前列腺癌组织学切片的数据（第一阶段）。 在第二阶段，NanoCytomics将开发标准操作程序，并将开发改进的生物标志物，可以更准确地识别临床显著的前列腺癌。在II期，我们还将通过对诊断为前列腺癌的男性在索引活检后3至10年临床随访后进行直肠切除术的存档索引活检进行PWS，验证独立数据集上的生物标志物。我们的目标是，到项目完成时，该技术将得到充分开发，进行临床测试，并为FDA试验和临床使用做好准备。

 DESCRIPTION (provided by applicant): Prostate cancer is the leading cancer among U.S. men. The biggest limitation of current prostate cancer management is that currently it is essentially impossible to accurately prognosticate which patients harbor aggressive cancers that progress into a metastatic disease and need treatment and which patients have non- aggressive indolent cancers that would not pose harm. Currently available techniques to progrnosticate prostate cancer suffer from lack of clinical utility, high cost and/or lack of sensitivity. We propse a new paradigm to accurately identify patients harboring aggressive versus non-aggressive disease among men with prostate cancer managed with active surveillance (repeat biopsies every 1-3 years). We propose to achieve this by detecting prostate field carcinogenesis, which is the notion that the genetic or environmental milieu that results in carcinogenesis impacts upon the entire prostate. Hence, not only tumor cells but also a much larger population of cells throughout the prostate which otherwise would appear normal on a biopsy - bear the fingerprint of the risk of aggressive cancer. Some of the first alterations that develop in cells in field carcinogenesis are at the nanoscale level and are too small to be detected by conventional microscopy, as with a pathologist examining prostate biopsies. We have developed a new optical technology, Partial Wave Spectroscopic (PWS) microscopy (or simply, nanocytology), which is uniquely suited to detect these subtle alterations in field carcinogenesis. We have validated nanocytology in prior clinical trials in seven types of cancer (lung, colon, prostate, ovarian, esophageal, pancreatic, and thyroid) in 759 patients. In a recent study of prostate cancer patients with Gleason 6 disease undergoing Active Surveillance (n = 38), we found that PWS nanocytology performed on histologically normal prostate epithelium was able to successfully predict subsequent progressors versus non-progressors. In the future, we envision that nanocytology can be coupled into existing prostate cancer care. The patients with prostate cancer who already undergo active surveillance will have their biopsies examined via PWS nanocytology, which will identify patients with aggressive versus non-aggressive tumors. In order to achieve this goal, as part of this SBIR Fast-track application NanoCytomics will first develop a fully-automated, whole-slide, fast PWS nanocytology system that is specifically optimized to acquire data on prostate cancer histological sections (Phase I). In Phase II, NanoCytomics will develop standard operating procedures and will develop improved biomarkers that can more accurately identify clinically significant prostate cancer. In Phase II, we will also validate the biomarkers on an independent data set by performing PWS on archival index biopsies in men diagnosed with prostate cancer who have had a prostatectomy after 3 to 10 years of clinical follow-up after the index biopsy. Our goal is that by the time the project is completed the technology will be fully developed, clinically tested and ready for FDA trials and clinical use.