Developing a genomic approach for cancer screening

描述（由申请人提供）：通过筛查早期发现癌症已被证明可以提高几种常见恶性肿瘤的生存率。然而，筛查伴随着巨大的风险和费用。所有筛查测试面临的一个重要问题是，在尽可能多地发现癌症的同时，尽量减少假阳性的发现。假阳性筛查结果会引起患者及其家属的焦虑，需要额外昂贵的检查，如果后续研究导致并发症，可能会造成伤害。我们建议开发一种新的癌症筛查基因组方法，利用从癌症基因组高通量重测序中获得的见解。我们将在肺癌的背景下开发这种方法，因为肺癌是癌症死亡的头号原因，而且低剂量计算机断层扫描（CT）筛查最近已被证明对高危患者的生存有显著的好处。然而，低剂量CT肺癌筛查中约95%的阳性筛查结果是假阳性，因此显然需要改进。这个建议描述了我们开发、优化和测试我们的方法的计划。我们将进行临床前和临床评估，并将在多种情况下测试我们的方法，包括作为区分真阳性和假阳性筛查结果的二次筛查程序，以及作为主要筛查方式。重要的是，该方法很容易扩展到任何具有高通量测序数据的癌症，我们设想最终能够使用单一分析筛选大多数常见癌症。

DESCRIPTION (provided by applicant): Early detection of cancer via screening has been shown to lead to improved survival for several common malignancies. However, screening comes with significant risks and expenses. One important issue faced by all screening tests is detecting as many cancers as possible while minimizing identification of false positives. False positive screening results induce anxiety in patients and their families, require additional expensive tests, and may result in harm if a follow-up study leads to a complication. We propose to develop a novel, genomic approach for cancer screening that leverages insights gained from high throughput re-sequencing of cancer genomes. We will develop this method in the context of lung cancer, since it is the number one cause of cancer deaths and since low dose computed tomography (CT) screening has recently been shown to produce significant survival benefits in high-risk patients. However, ~95% of positive screening results from low dose CT lung cancer screenings are false positives and so improvements are clearly needed. This proposal describes our plan to develop, optimize, and test our method. We will perform both pre-clinical and clinical evaluations and will test our approach in multiple settings, includig as a secondary screening procedure for differentiating between true positive and false positive screening results and as a primary screening modality. Importantly, the method is readily extendable to any cancer for which high throughout sequencing data are available and we envision ultimately being able to screen for most common cancers using a single assay.