Earlier Detection of Cancers using Non-Plasma Based Liquid Biopsies

项目总结/摘要 癌症的早期检测提供了降低癌症相关发病率和癌症风险的最有效方法之一。 mortality.不幸的是，癌症的早期检测受到几个因素的阻碍，包括缺乏合适的药物。 测试和成本。个性化医疗和技术进步正在改变治疗癌症的方法 诊断.基于血液的液体活检为早期检测试验的发展提供了机会。 然而，大多数恶性肿瘤没有有效的微创策略进行早期检测， 使用基于血液的测定不容易检测肿瘤前或肿瘤状态。的一个主要 开发微创测试的挑战是识别适当的生物流体和癌症 特定的生物标志物。在过去的二十年里，从癌细胞中释放的DNA已经成为一种特异性的 癌症的临床生物标志物。我们以前已经开发了敏感的方法来检测这种释放 肿瘤DNA（rtDNA），并展示了其在各种临床样品中的潜在应用。我们有 广泛的初步结果表明，与某些癌症相关的生物流体显着富集在rtDNA 与血相比。我们的研究小组已经开发出灵敏的方法来检测和定量RTDNA， 大量的生物液体此外，我们集团与工业合作伙伴PapGene Inc. 该公司已经参与了液体活检应用的临床开发。该项目将建立在 这些优势，以开发测试检测脑，头和颈部，和结肠癌的脑脊液 分别为液体、唾液和粪便。一种非血浆液体活检方法用于早期检测 在血液中难以检测的癌症或癌前病变将代表重大的医学进步。

PROJECT SUMMARY/ABSTRACT Early detection of cancer provides one of the most effective ways to reduce cancer related morbidity and mortality. Unfortunately, early detection of cancers is hindered by several factors, including the lack of suitable tests and cost. Personalized medicine and technological advances are changing the approach to cancer diagnosis. Blood based liquid biopsy has provided an opportunity for the development of early detection tests. However, most malignancies do not have effective minimally invasive strategies for early detection and certain pre-neoplastic or neoplastic conditions are not readily detectable using blood based assays. One of the chief challenges in developing minimally-invasive tests is the identification of the appropriate biofluid and cancer specific biomarkers. Over the past two decades, DNA released from cancer cells has emerged as a specific clinical biomarker of cancer. We have previously developed sensitive methods for detection of this released tumor DNA (rtDNA) and demonstrated its potential applications in variety of clinical samples. We have extensive preliminary results that biofluids associated with certain cancers are significantly enriched in rtDNA when compared to blood. Our group has developed sensitive methods to detect and quantify rtDNA in numerous biofluids. In addition, our group has an ongoing relationship with an industrial partner, PapGene Inc that has already participated in the clinical development of liquid biopsy applications. This project will build on those strengths to develop tests for the detection of brain, head and neck, and colon cancers in cerebrospinal fluid, saliva, and stool, respectively. A non-plasma based liquid biopsy approach for the earlier detection of cancers or premalignant lesions difficult to detect in the blood would represent a significant medical advance.