Circulating Biomarker Consortium for Pancreatic Cancer Early Detection

项目摘要（不超过30行文本）： 胰腺癌是美国癌症死亡的第四大原因。 无法治愈的疾病，绝大多数人活不到12个月。胰管癌的高死亡率 腺癌（PDAC）是胰腺癌最常见的形式，主要是诊断的结果 在晚期，当肿瘤不再可切除以治愈时。然而，症状很少发展， 早期疾病，以及PDAC的既定风险因素，如吸烟，肥胖，慢性胰腺炎， 糖尿病和PDAC家族史不足以对人群进行疾病筛查的风险分层。 实验研究表明，从创始人恶性克隆的形成开始， 与病人的诊断相关联，这意味着早期发现的机会之窗。然而，不早 检测标记物已经发展到临床使用，部分原因是几乎没有基础设施被开发， 有利于对有前途的候选人进行严格的调查。为了实现PDAC早期检测的关键目标， 我们将具有长期合作创新记录的研究人员聚集在一起， 胰腺癌循环生物标志物（Pan-C2-Bio）联盟。在这个联盟中，我们加入了正在进行的 在五个大型癌症中心收集患者生物标本，并进行四次非常有希望的早期检测 技术和复杂的计算机建模来定义非侵入性PDAC筛查策略。的 联盟将努力实现三个主要目标：（1）生成一个大的，统一的，彻底注释 用于测试早期检测标志物的人类和小鼠样品库，（2）确定性评估四种高度 有前途的PDAC早期检测标记物，用于近期临床应用，包括循环无细胞DNA 突变和甲基化模式、癌症来源的外来体和代谢标志物，以及（3）鉴定 基于生物标志物的筛查策略，以促进高危人群和一般人群的早期癌症诊断， 人口因此，泛C2生物联盟提出的工作将提供急需的生物标本 早期检测研究的资源，提供证据支持（或反对）四个非常有前途的PDAC的效用 早期检测技术，并展示新的生物标志物如何与以前的生物标志物相结合。 特征的风险因素，以确定个人的疾病筛查。通过这项工作，我们希望减少 胰腺癌的死亡率，通过确定那些处于最高风险和诊断亚临床疾病时， 可以应用治愈性疗法。

PROJECT SUMMARY (no more than 30 lines of text): Pancreatic cancer is the fourth-leading cause of cancer death in the U.S. Over 80% of patients present with incurable disease, and the vast majority live for <12 months. The high mortality of pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is largely a consequence of diagnosis at an advanced stage when the tumor is no longer resectable for cure. However, symptoms rarely develop with early disease, and established risk factors for PDAC, such as tobacco smoking, obesity, chronic pancreatitis, diabetes, and family history of PDAC, are insufficient to risk stratify the population for disease screening. Experimental studies indicate that more than a decade elapses from formation of the founder malignant clone to a patient's diagnosis, suggesting a window of opportunity for early detection. Nevertheless, no early detection markers have advanced to clinical use, in part, because little infrastructure has been developed to facilitate rigorous investigation of promising candidates. To address the critical goal of PDAC early detection, we have brought together investigators with a long track-record of collaborative innovation to form the Pancreatic Cancer Circulating Biomarker (Pan-C2-Bio) Consortium. Within this Consortium, we join ongoing patient biospecimen collection at five large cancer centers with four highly promising early detection technologies and sophisticated computer modeling to define a non-invasive PDAC screening strategy. The Consortium will work to achieve three primary goals: (1) generation of a large, unified, thoroughly-annotated human and murine sample bank for testing of early detection markers, (2) definitive evaluation of four highly promising PDAC early detection markers for near-term clinical utility, including circulating cell-free DNA mutations and methylation patterns, cancer-derived exosomes, and metabolism markers, and (3) identification of biomarker-based screening strategies to facilitate early cancer diagnosis in high-risk groups and the general population. Thus, the work proposed by the Pan-C2-Bio Consortium will deliver much-needed biospecimen resources for early detection studies, provide evidence for (or against) the utility of four highly promising PDAC early detection technologies, and demonstrate how new biomarkers can be integrated with previously characterized risk factors to identify individuals for disease screening. With this work, we look to reduce mortality from pancreatic cancer by identifying those at highest risk and diagnosing subclinical disease when curative therapies can be applied.