Multi-analyte Approach for Earlier Detection of Cancers in Non Plasma Biofluids

项目摘要 早期发现癌症是减少癌症相关疾病的最有效方法之一。 发病率和死亡率。然而，大多数恶性肿瘤，包括脑和头颈部， 癌症没有有效的早期检测微创策略。不幸的是， 早期发现受到几个因素的阻碍，包括缺乏适当的测试和成本。一 开发非侵入性测试的主要挑战之一是识别适当的 生物流体和特定标记物。虽然基于血液的检测显示出了希望，但许多癌症仍然存在。 在流通中不易被发现。在过去的二十年里，从癌症中释放出来的DNA 细胞已经成为癌症的特异性生物标志物。我们以前开发了敏感的 用于从少量样品中同时检测多种基于DNA的分析物的方法， 各种生物标本中的起始材料。我们有广泛的初步结果， 与某些癌症相关的生物流体，如脑脊液（CSF）和唾液， 与血液相比，释放的肿瘤DNA（rtDNA）显着富集。此外，我们集团 与工业合作伙伴保持着持续的关系，将我们有前途的技术转化为 临床领域。该提案将建立在这些优势的基础上，开发针对 - 在CSF和唾液中灵敏和特异地检测脑和头颈癌， 分别一种用于癌症早期检测的非血浆“液体活检”方法 在血液中难以检测到，这将代表一个重大的医学进步。

PROJECT SUMMARY Early detection of cancer provides one of the most effective ways to reduce cancer related morbidity and mortality. However, most malignancies including brain and head and neck cancers do not have effective minimally invasive strategies for early detection. Unfortunately, early detection is hindered by several factors, including the lack of suitable tests and cost. One of the chief challenges in developing non-invasive tests is the identification of the appropriate biofluid and specific markers. While blood-based testing has shown promise, many cancers are not easily detected in the circulation. Over the past two decades, DNA released from cancer cells has emerged as a specific biomarker of cancer. We have previously developed sensitive methods for the simultaneous detection of multiple DNA based analytes from a small quantity of starting material in a variety of biospecimens. We have extensive preliminary results that biofluids, such as cerebrospinal fluid (CSF) and saliva, associated with certain cancers are significantly enriched in released tumor DNA (rtDNA) compared to blood. In addition, our group has an ongoing relationship with an industrial partner to translate our promising technology into the clinical realm. This proposal will build on those strengths to develop assays for the sensitive and specific detection of brain and head and neck cancer in CSF and saliva, respectively. A non-plasma based “liquid biopsy” approach for the earlier detection of cancers difficult to detect in the blood would represent a significant medical advance.