NanoCytology to mitigate overdiagnosis of prostate cancer

 描述(申请人提供)：前列腺癌是美国男性的头号癌症。目前前列腺癌治疗的最大局限性是，目前基本上不可能准确预测哪些患者患有侵袭性癌症，发展为转移性疾病需要治疗，哪些患者患有非侵袭性惰性癌症，不会造成伤害。目前用于预测前列腺癌的现有技术存在着缺乏临床实用性、成本高和/或缺乏敏感性的问题。我们提出了一个新的范例来准确地识别前列腺癌男性患者中存在侵袭性和非侵袭性疾病的患者，这些患者接受了积极的监测(每1-3年重复活检一次)。我们建议通过检测前列腺场癌变来实现这一点，这是一个概念，即导致癌变的遗传或环境环境对整个前列腺产生影响。因此，不仅是肿瘤细胞，而且整个前列腺中更多的细胞群，否则在活组织检查中看起来是正常的-带有侵袭性癌症风险的指纹。在实地致癌过程中，细胞中最早发生的一些变化是纳米级的，太小了，无法用传统的显微镜检测到，就像病理学家检查前列腺活检一样。我们开发了一种新的光学技术，部分波谱(PWS)显微镜(或简称纳米细胞学)，它唯一适合于检测现场致癌过程中的这些细微变化。我们已经在759名患者的七种癌症(肺癌、结肠癌、前列腺癌、卵巢癌、食道癌、胰腺癌和甲状腺癌)的临床试验中验证了纳米细胞学。在最近一项对患有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PWS纳米细胞学检查能够成功地预测后续的进展者与非进展者。在未来，我们设想纳米细胞学可以与现有的前列腺癌治疗相结合。已经接受积极监测的前列腺癌患者将通过PWS纳米细胞学进行活检检查，这将识别侵袭性肿瘤和非侵袭性肿瘤的患者。为了实现这一目标，作为SBIR快速跟踪应用的一部分，NanoCytomics公司将首先开发一种全自动、全载玻片、快速PWS纳米细胞学系统，该系统专门为获取前列腺癌组织切片数据而优化(第一阶段)。在第二阶段，NanoCytomics将开发标准操作程序，并将开发能够更准确地识别具有临床意义的前列腺癌的改进的生物标记物。在第二阶段，我们还将验证独立数据集上的生物标志物，方法是对被诊断为前列腺癌的男性进行PWS，这些患者在指数活检后进行了3到10年的临床随访后接受了前列腺切除术。我们的目标是，到该项目完成时，该技术将得到全面开发、临床测试，并准备好供FDA试验和临床使用。

 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.