Translating buccal nanocytology for lung cancer screening into clinical practice

项目摘要 学术产业伙伴关系赠款的总体目标是制定人口风险分层 这是一种有效且具有成本效益的肺癌筛查工具。肺癌代表了一种理想 筛查的恶性肿瘤，因为其患病率，可识别的风险组（当前/既往吸烟者）和 如果早期诊断，手术治愈疾病的能力。然而，没有可靠的筛选技术 低剂量CT（LDCT）扫描等选择充满了成本和大量错误的危害， 积极因素。为了使肺癌筛查可行，当务之急是开发一种测试来预先筛查 通过识别可能患有肺癌并将从LDCT中获益的患者亚组来进行LDCT。 该测试必须对早期疾病（例如I期）敏感，成本低，并且能够在初级保健中进行 设置.这个项目的目标就是开发这样一个测试。一种有吸引力的方法是利用 致癌作用，这一概念，即相同的遗传/环境，导致病变的一个领域， 肺将影响整个空气消化道粘膜。颊（颊）粘膜是一面“分子镜子” 尽管目前的技术不足以将这种现象转化为一种新的癌症， 最小侵入性筛选试验。初步数据显示， 口腔细胞对野外致癌作用非常敏感，因此可以作为肺肿瘤的生物标志物。 癌这些纳米结构的变化可以通过一种实用且高度准确的方式检测到， 新的生物光子学技术，分波光谱（PWS）显微镜（“纳米细胞学”）。在本研究中， PWS技术将得到改进，并根据PWS可检测的纳米尺度开发预测规则 这是针对早期可治愈肺癌的优化改变。拟议项目的目标是完成 剩下的技术开发方面，将纳米细胞学转化为实用的，准确的，低成本的， 成本测试，使其达到可行的人群筛查水平，并进行预先确定的临床试验。 验证。该团队设想，在完成这个项目后，纳米细胞学将准备一个明确的 临床试验导致临床实践的启动。这种新的范式可以改变临床实践， 肺癌筛查，从而减轻这种恶性肿瘤在美国人中的大量死亡。

Project Summary The overarching goal of the Academic Industrial Partnership grant is to develop a population risk-stratification tool that will allow efficacious and cost-effective lung cancer screening. Lung cancer represents an ideal malignancy for screening because of its prevalence, identifiable risk groups (current/former smokers) and ability to surgically cure the disease if diagnosed early. However, there are no robust screening techniques with options such as low-dose CT (LDCT) scans fraught with cost and harm from large numbers of false positives. In order to make lung cancer screening viable, it is imperative to develop a test to pre-screen for LDCT by identifying the subset of patients who are likely to harbor lung cancers and would benefit from LDCT. The test must be sensitive to early disease (e.g. Stage I), low-cost, and able to be carried out in a primary care setting. The goal of this project is to develop such a test. One attractive approach is to exploit field carcinogenesis, the concept that the same genetic/environmental milieu that results in a lesion in one area of the lung will impact upon the entire aero digestive mucosa. The buccal (cheek) mucosa is a “molecular mirror” of lung carcinogenesis, although current techniques are inadequate to translate this phenomenon into a minimally intrusive screening test. The preliminary data show that the alteration of nanoscale architecture in buccal cells is exquisitely sensitive to field carcinogenesis and hence may serve as a robust biomarker for lung cancer. These nano-architectural changes can be detected in a practical and highly accurate fashion via a novel biophotonics technology, partial wave spectroscopic (PWS) microscopy (“nanocytology”). In this study, PWS technology will be refined and a prediction rule developed based on the PWS-detectable nanoscale alterations that is optimized for early stage, curable lung cancer. The goal of the proposed project is to finalize the remaining technology development aspects to translate nanocytology into a practical, accurate, and low- cost test, bring it to the point where it is viable for population screening, and conduct a pre-definitive clinical validation. The team envision that upon completion of this project, nanocytology will be ready for a definitive clinical trial leading to a launch in clinical practice. This novel paradigm could transform the clinical practice of lung cancer screening and thereby mitigate the large toll of this malignancy in Americans.