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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

基本信息

批准号：
9757724
负责人：
ANN M KILLARY
金额：
$ 88.32万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
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/9757724
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

项目摘要

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.

项目总结