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: 9490551
• 负责人: ANN M KILLARY
• 金额: $ 94.05万
• 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/9490551
• 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; Smoking; Specimen; Symptoms; Technology; Testing; Tissues; Validation; advanced disease; base; biomarker discovery; biomarker identification; biomarker panel; biomarker validation; candidate marker; chronic pancreatitis; circulating biomarkers; clinical phenotype; cohort; curative treatments; design; early detection biomarkers; exosome; functional genomics; high risk; imaging modality; improved; innovation; microRNA biomarkers; migration; non-invasive imaging; novel; population based; prospective; screening; 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.

项目摘要 胰腺癌的早期检测迫切需要生物标志物。然而，单个分子 具有基于人群的筛查所需的灵敏度和特异性。CA-19-9 已经被广泛研究，但未能证明早期诊断所需的预测价值。 检测和诊断。尽管有许多平台，包括蛋白质组学、基因组学和转录组学 尽管已经利用了多种方法并且鉴定了生物标志物候选物，但是还没有一种平台或分子被 在大型盲态人群筛选中成功验证。我们采用了功能性基因组途径 靶向胰腺和其他组织中改变的最早基因组间隔的生物标志物发现方法 吸烟相关的癌症，重点是参与关键癌症相关细胞通路的生物标志物。我们 我已经确定了一个“迁移特征”和生物标志物面板，该面板已经过两次设盲验证 包括NCI-EDRN胰腺癌早期疾病和良性健康参考集 对照结果表明，我们的生物标志物组提高了CA 19 -9检测 无症状早期胰腺癌在验证平台上产生显著结果。我们有 开发了胰腺癌的血浆miRNA生物标志物组，并在多项试验中验证了这些。的 我们的生物标志物组合显示出检测早期胰腺癌的高灵敏度和特异性。 癌我们将进一步完善这一早期生物标志物组和一种新的风险评分方法， 一般人群和高危人群进行筛查。将在大型回顾性会议上对精制面板进行验证 以及根据ProBE设计早期检测胰腺癌的前瞻性队列。以便我们 为了在转移之前鉴定早期疾病，并进行治疗性干预，我们将利用小鼠- 从血浆和血浆外来体开发整合生物标志物谱以检测晚期 在晚期癌症发展之前的前体阶段PanIN，随后验证了 诊断前生物标志物组。我们还将开发一种新的两层筛选策略， 生物标志物和新的成像工具，以改变临床管理计划，并显着提高生存率 最致命的癌症之一