Circulating Biomarkers and Imaging for Early Detection of Pancreatic Cancer

The overall goal of this renewal application is to validate biomarker signatures associated with aberrantly expressing pathways in pancreatic cancer for early stage PDAC detection among asymptomatic patients with high risk clinical, genetic and/or familial susceptibility characteristics. PDAC early detection signatures, developed with circulating transcriptomics, proteomics and metabolomics (omics) biomarkers identified in the first funding cycle, will be characterized for their association with heterogeneous disease subtypes and integrated with imaging-based disease subtype features derived with machine learning methods from CT/MRI scans reflecting functional changes in malignant lesions of the pancreas. Integration of Omics data with CT imaging features will be done by developing Multimodal Integrative Analytical Models (MIAM) predictive of early stage pancreatic cancer. Together, the pathway-based biomarker panels integrated with CT imaging data will define a novel clinically significant strategy for early detection and risk stratification. During the first funding cycle, a number of omics based circulating biomarkers were developed and validated in multiple sample cohorts from patients with early stage resectable disease. These together with additional candidate biomarkers in the pipeline will be further validated and investigated for their association with disease subtypes in Phases II, III and IV studies according to PRoBE-design in the renewal application. For phase IV studies, performance of the biomarkers in detecting disease and predicting clinical outcomes among asymptomatic patients and at-risk individuals will be ascertained with retrospective and prospective longitudinal pre-diagnostic sample cohorts, including one representing the underserved population. The innovative statistical approach of MIAM will be shared with other members of the consortia for rigorous validation and in the long term, we hope to translate the findings into developing open source software for use in clinical diagnostic laboratories in the future. Specific Aims of the PCDC grant are: Aim 1: Validation of pathway-associated biomarker signatures and novel CT imaging features for molecular subtype-related early stage PDAC and development of MIAM to integrate approaches for detection of early stage PDAC in Phase II cohorts. Aim 2: Validation of circulating Omics biomarkers and integration with precision imaging features in Phase III retrospective longitudinal pre-diagnostic cohorts for early detection and risk assessment. Aim 3: Prospective Screening and Validation of biomarker panels in Phase IV High Risk CohortsAim 4: Participate in collaborative projects with other PCDC-RUs by sharing data/ideas and contribute in building biorepository and assay development using our unique technical and a