To achieve the goals of the Pancreatic Cancer Detection Consortium (PCDC), we will leverage Mayo Clinicresearch registries, biorepositories, and our pancreatic neoplasia practice to develop a resource forcollaborative research aimed at improved detection of early stage pancreatic ductaladenocarcinoma (PDAC) and its precursors. Mayo Clinic is an established center of excellence forresearch in pancreatic conditions, and its ongoing biospecimen resources contain blood samples from ultra-rapidly identified and prospectively enrolled PDAC patients (n=3,092); high risk members in familialpancreatic kindreds (n=2,575); patients with high risk pancreatic conditions (n=1,599); and healthy controls(n=2,791). We will introduce longitudinal biospecimen collection from subjects to validate biomarkerperformance in various settings. Innovatively identified biomarkers will be evaluated: using cellreprogramming of late stage human PDAC generated cells, the Zaret lab found that, when re-differentiated,underwent early stages of PDAC leading to new candidate biomarkers, including THBS2; the Ahlquist labidentified novel methylated DNA markers for PDAC and high grade dysplasia using unbiased wholemethylome sequencing. Our Specific Aims are to: (1) Construct formal biospecimen sets from DNA,serum, or plasma suitable for PRoBE Phase 2 and 3 biomarker validation studies. We will use existingresources and also prospectively collect blood and pancreatic juice every 1-2 years from patients withpancreatic cysts; we will collect blood every 2 years from existing and prospectively recruited high risk familymembers >age 50. (2) Validate serum or plasma biomarkers for early detection of pancreatic canceras directed by the evidence and PCDC consensus in Phase 2 and 3 studies. We will perform a Phase 3validation of THBS2 and CA19-9 suitable for the primary care setting using PLCO samples. We will performa Phase 2 validation of THBS2 and CA19-9 suitable for a pancreatology clinic setting of high risk subjects todiscriminate PDAC from chronic pancreatitis, cystic neoplasms, or neuroendocrine tumors. We will performa Phase 2 validation of a panel of methylated DNA markers (including ADCY1, CD1D, BMP3, CLEC11A,TWIST1, ELMO) to discriminate healthy subjects from PDAC patients. (3) Perform a Phase 2 study tovalidate biomarkers for early detection of pancreatic cancer or high grade dysplasia in patients withpancreatic cysts. We will examine the DNA methylation markers (including ZNF781, PRKCB, CD1D,BMP3, CLEC11A, HOXA, ELMO) that discriminate low grade dysplasia from high grade dysplasia in IPMN.We will validate a panel of these biomarkers in prospectively collected plasma and pancreatic juice ofpancreatic cyst patients. Our resources and experience are extensive, from a depth of biobankingexperience and biospecimens to epidemiology, gastroenterology, novel biomarker development, andbiostatistics expertise relevant to early detection and biomarker validation in PDAC.
|Effective start/end date||7/15/16 → 6/30/21|
- National Institutes of Health: $644,076.00
- National Institutes of Health: $238,500.00