COLORECTAL CANCER (CRC) SCREENING VIA RECTAL NANOCYTOLOGY

描述(由申请者提供)：这项小型企业创新研究基金的目标是开发一种高精度、微创的结直肠癌风险分层技术并将其商业化，该技术非常简单，可以由初级保健提供者在年度体检期间进行。尽管现有的指南建议对所有50岁以上的患者进行结直肠癌筛查(&gt；1亿美国人)，但结直肠癌仍然是癌症死亡的第二大原因。这在一定程度上是由于包括结肠镜检查在内的现有结直肠癌筛查技术的局限性，结肠镜检查被认为是结直肠癌筛查的“黄金标准”。这是因为由于各种原因，包括费用、患者不情愿、并发症和内窥镜检查人员数量不足，只有一小部分符合条件的人群接受结肠镜检查。此外，目前对“平均风险”人群的结肠镜检查非常低效，因为只有6%的筛查人群有明显的肿瘤(晚期腺瘤)。因此，开发一种微创测试来识别哪些患者患有结肠腺瘤，哪些患者不患有结肠腺瘤，对于更好地定位结肠镜检查对象至关重要。这将使首次能够在全人口范围内筛查CRC。西北大学和北岸大学医疗系统的一个由工程师、生物学家和临床医生组成的跨学科团队已经开发出部分波谱(PWS)显微镜，这是一种新的生物光子学技术，能够感知在其他细胞病理学正常的粘膜细胞中遗传/表观遗传变化的纳米级细胞内结构相关性。初步的动物和人类研究表明，PWS显微镜有可能检测到细胞学上看起来正常的细胞的细微变化，这是由于 癌症/癌前病变存在于器官的不同部位，这是公认的野外致癌概念的结果。这使得通过直肠黏膜细胞的PWS分析来检测结肠肿瘤的存在成为可能，通过简单的细胞刷检就可以很容易地获得这些细胞，而不需要结肠镜或肠道准备。事实上，在对146名患者的初步研究中，人们注意到，来自内窥镜下正常直肠黏膜刷检的PWS标记物反映了结肠其他部位肿瘤性病变的重要性(晚期腺瘤和腺瘤&无肿瘤)。在未来直肠PWS分析的最终临床验证之前，有几个步骤是必需的。在这项SBIR的第一阶段，将开发具有高通量能力的自动PWS显微镜，并测试其纳米级的灵敏度和诊断潜力。在第二阶段，a 将制定标准操作程序，以优化样品收集、样品处理和PWS分析算法。自动PWS系统和SOP将在300名患者(训练集，n=200和验证集，n=100)上进行测试。成功的SBIR研究将使NanoCytomics能够创建一种商业上可行的诊断系统，这对未来的多中心临床试验和FDA的批准至关重要。

DESCRIPTION (provided by applicant): The goal of this small business innovation research grant is to develop and commercialize a highly accurate, minimally invasive risk stratification technique for colorectal cancer (CRC) that is simple enough to be performed by the primary care provider during an annual physical exam. Although existing guidelines recommend CRC screening for all patients over age 50 (>100 million Americans), CRC remains the second leading cause of cancer death. This is in part due to the limitations in the existing CRC screening techniques including colonoscopy which is considered a 'gold standard' for CRC screening. This is because only a small fraction of eligible population undergoes colonoscopy due to variety of reasons including expense, patient reluctance, complications, and insufficient number of endoscopists. Furthermore, the current practice of colonoscopy on the "average risk" population is remarkably inefficient as only ~6% of the screening population have significant neoplasia (advanced adenomas). Hence developing a minimally invasive test to identify patients who do and do not harbor colonic adenomas is of crucial importance to better target patients for colonoscopy. This would enable, for the first time, a population wide screening for CRC. An interdisciplinary team of engineers, biologists and clinicians at Northwestern University and Northshore University HealthSystem has developed Partial Wave Spectroscopic (PWS) Microscopy, a novel biophotonic technique that enables sensing the nanoscale intracellular architectural correlates of the genetic/epigenetic changes in otherwise cytopathologically normal mucosa cells. Preliminary animal and human studies demonstrated the potential of PWS microscopy to detect subtle alterations in cytologically normal-appearing cells that are due to the presence of cancerous/precancerous lesions present in a different part of an organ, a consequence of the well-established concept of field carcinogenesis. This opens a possibility to detect the presence of colonic neoplasia by means of PWS analysis of cells from rectal mucosa, which is readily accessible by a simple brushing of the cells without the need for colonoscopy or bowel preparation. Indeed, in pilot studies on 146 patients it was noted that the PWS marker from endoscopically-normal rectal mucosal brushings mirrored the significance of neoplastic lesions elsewhere in the colon (advanced adenomas > adenomas > no neoplasia). There are several steps that are required prior to the future definitive clinical validation of rectal PWS analysis. In phase I of this SBIR, an automated PWS microscopy with high throughput capability will be developed and tested for its nanoscale sensitivity and diagnostic potential. In phase II, a standard operating procedure will be developed that will optimize the sample collection, sample processing and PWS analysis algorithms. The automated PWS system and the SOP will be tested on 300 patients (training set, n = 200 and validation set, n = 100). The successful SBIR research would enable NanoCytomics to create a commercially viable diagnostic system that would be critical for future multi-center clinical trials and FDA approval.