Earlier Detection of Cancers using Non-Plasma Based Liquid Biopsies

项目摘要/摘要 早期发现癌症是减少癌症相关发病率的最有效方法之一 死亡率。不幸的是，癌症的早期发现受到几个因素的阻碍，包括缺乏合适的 测试和成本。个性化医学和技术进步正在改变癌症的治疗方法 诊断。以血液为基础的液体活组织检查为发展早期检测试验提供了机会。 然而，大多数恶性肿瘤没有有效的微创策略来早期发现和某些 使用基于血液的化验不容易发现肿瘤前期或肿瘤的情况。其中一位酋长 开发微创测试的挑战是识别合适的生物液和癌症 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已经成为一种特殊的 癌症的临床生物标志物。我们之前已经开发了敏感的方法来检测这种释放的 肿瘤DNA(RTDNA)，并展示了其在各种临床标本中的潜在应用。我们有 广泛的初步结果表明，与某些癌症相关的生物液中的rtDNA显著丰富 与鲜血相比。我们团队已经开发出灵敏的方法来检测和定量 大量的生物体液。此外，我们集团还与行业合作伙伴Papgene Inc.保持着持续的关系 它已经参与了液体活组织检查应用的临床开发。这个项目将建立在 这些优势可用于脑脊液中脑癌、头颈部癌和结肠癌的检测 分别是液体、唾液和大便。一种非血浆液体活检法早期检测食管瘤 血液中难以检测到的癌症或癌前病变将代表着一项重大的医学进步。

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.