COLORECTAL CANCER (CRC) SCREENING VIA RECTAL NANOCYTOLOGY

描述（申请人提供）：这项小型企业创新研究资助的目标是开发和商业化一种高度准确的、微创的结直肠癌（CRC）风险分层技术，该技术简单到可以由初级保健提供者在年度体检中进行。（> 1亿美国人），CRC仍然是癌症死亡的第二大原因。这部分是由于现有CRC筛查技术的局限性，包括结肠镜检查，结肠镜检查被认为是CRC筛查的“金标准”。这是因为只有一小部分符合条件的人群由于各种原因（包括费用、患者不情愿、并发症和内窥镜医生数量不足）而接受结肠镜检查。此外，目前对“平均风险”人群进行结肠镜检查的做法是非常低效的，因为只有约6%的筛查人群具有显著的瘤形成（晚期腺瘤）。因此，开发一种微创检测来识别患有和不患有结肠腺瘤的患者对于更好地靶向患者进行结肠镜检查至关重要。这将首次实现对CRC的全人群筛查。西北大学和Northshore University HealthSystem的工程师，生物学家和临床医生组成的跨学科团队开发了部分波光谱（PWS）显微镜，这是一种新型的生物光子技术，能够感测在其他细胞病理学正常粘膜细胞中遗传/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显微镜检测细胞学正常细胞的细微变化的潜力，这些细胞学正常细胞是由于 在器官的不同部分存在癌性/癌前病变，这是公认的现场致癌概念的结果。这开启了通过来自直肠粘膜的细胞的PWS分析来检测结肠瘤形成的存在的可能性，其通过简单刷取细胞而容易获得，而不需要结肠镜检查或肠道准备。事实上，在对146名患者的初步研究中，注意到来自内窥镜检查正常的直肠粘膜刷检的PWS标记反映了结肠其他部位肿瘤病变的重要性（晚期腺瘤>腺瘤>无肿瘤）。在直肠PWS分析的未来确定性临床验证之前，需要几个步骤。在SBIR的第一阶段，将开发具有高通量能力的自动PWS显微镜，并测试其纳米级灵敏度和诊断潜力。第二阶段a 将制定标准操作程序，以优化样本采集、样本处理和PWS分析算法。将在300例患者（训练集，n = 200，验证集，n = 100）中测试自动PWS系统和SOP。成功的SBIR研究将使NanoCytomics能够创建一个商业上可行的诊断系统，这对未来的多中心临床试验和FDA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.