Circulating Biomarkers and Imaging for Early Detection of Pancreatic Cancer

用于早期检测胰腺癌的循环生物标志物和成像

• 批准号: 10227791
• 负责人: ANN M KILLARY
• 金额: $ 77.21万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-07 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227791
• 关键词: Advanced Development; Advanced Malignant Neoplasm; Age; Age-Years; Applications Grants; Benign; Biological Markers; Blinded; Blood; CA-19-9 Antigen; Cancer Etiology; Cessation of life; Clinic; Clinical; Clinical Management; Collection; Core Biopsy; Detection; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Disease Progression; Early Detection Research Network; Early Diagnosis; Excision; Family history of; General Population; Genetically Engineered Mouse; Genomics; Goals; High-Risk Cancer; Human; Image; Imaging Device; Imaging Techniques; Incidence; Individual; Intervention; Lesion; Life; Longitudinal cohort; Malignant Neoplasms; Malignant neoplasm of pancreas; Mus; Neoplasm Metastasis; Operative Surgical Procedures; Organ; Pancreas; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraepithelial Neoplasia; Pathway interactions; Patients; Performance; Plasma; Population; Population Surveillance; Populations at Risk; Predictive Value; Prospective cohort; Proteomics; Resectable; Retrospective cohort; Risk; Sampling; Savings; Scheme; Sensitivity and Specificity; Specimen; Symptoms; Technology; Testing; Tissues; Validation; advanced disease; base; biomarker discovery; biomarker identification; biomarker panel; biomarker signature; biomarker validation; candidate marker; chronic pancreatitis; circulating biomarkers; clinical phenotype; cohort; curative treatments; design; detection method; early detection biomarkers; exosome; functional genomics; high risk; imaging modality; improved; innovation; microRNA biomarkers; migration; non-invasive imaging; novel; population based; prospective; screening; smoking-related cancer; tool; transcriptomics; tumor; tumor progression

PROJECT SUMMARY Biomarkers for the early detection of pancreatic cancer are urgently needed. However, individual molecules with the sensitivity and specificity needed for population-based screening have not been discovered. CA-19-9 has been studied extensively and yet has failed to demonstrate the predictive value necessary for early detection and diagnosis. Although many platforms, including proteomic, genomic and transcriptomic approaches have been utilized and biomarker candidates identified, no one platform or molecule has been successfully validated in large blinded population screens. We have taken a functional genomic pathways approach to biomarker discovery targeting the earliest genomic intervals altered in pancreatic and other smoking related cancers, focusing on biomarkers involved in critical cancer relevant cellular pathways. We have identified a “migration signature” and biomarker panel that has gone through two blinded validations including the NCI-EDRN pancreatic cancer reference set of early stage disease and benign and healthy controls. Results indicate that our panel of biomarkers improves the performance of CA19-9 to detect asymptomatic early stage pancreatic cancer yielding significant results across validations platforms. We have developed plasma miRNA biomarker panels for pancreatic cancer and validated these in multiple trials. The combination of our biomarkers demonstrates high sensitivity and specificity to detect early stage pancreatic cancer. We will further refine this early stage biomarker panel and a novel risk score approach to stratify the general population and at risk population for screening. Refined panels will be validated in large retrospective and prospective cohorts for early detection of pancreatic cancer according to ProBE design. In order that we identify early stage disease prior to metastasis, amenable to curative intervention, we will utilize a mouse- human approach to develop integrated biomarkers profiles from plasma and plasma exosomes to detect late precursor stage PanINs prior to development of advanced cancer with subsequent validation for a prediagnostic biomarker panel. We will also develop a novel two tiered screening strategy with validated biomarkers and novel imaging tools to change the clinical management plan and significantly improve survival of one of the most deadly cancers.

项目概要 然而，迫切需要用于早期检测胰腺癌的生物标志物。 尚未发现具有基于人群的筛查所需的敏感性和特异性的 CA-19-9。 已被广泛研究，但未能证明早期所需的预测价值 虽然有许多平台，包括蛋白质组、基因组和转录组。 已经使用了多种方法并确定了候选生物标志物，但尚未使用任何一种平台或分子 我们采用了功能基因组途径，并在大规模盲态人群筛选中成功得到验证。 针对胰腺和其他疾病中最早改变的基因组间隔的生物标志物发现方法 吸烟相关的癌症，重点关注参与关键癌症相关细胞途径的生物标志物。 已经确定了经过两次盲法验证的“迁移签名”和生物标记物组 包括早期疾病和良性健康的 NCI-EDRN 胰腺癌参考集 结果表明我们的生物标志物组提高了 CA19-9 的检测性能。 无症状早期胰腺癌在各个验证平台上都取得了显着的结果。 开发了用于胰腺癌的血浆 miRNA 生物标志物组，并在多项试验中对其进行了验证。 我们的生物标志物的组合显示出检测早期胰腺的高灵敏度和特异性 我们将进一步完善这个早期生物标志物组和一种新的风险评分方法来对癌症进行分层。 将对一般人群和高危人群进行筛查。精制的小组将在大型回顾性研究中得到验证。 以及根据 ProBE 设计进行胰腺癌早期检测的前瞻性队列。 为了识别转移前的早期疾病，并接受治疗性干预，我们将利用小鼠 人类方法从血浆和血浆外泌体中开发综合生物标志物谱以检测晚期 发展为晚期癌症之前的前兆阶段 PanIN，并随后验证 我们还将开发一种经过验证的新型两级筛查策略。 生物标志物和新型成像工具可改变临床管理计划并显着提高生存率 最致命的癌症之一。