(no more than 30 lines of text): Pancreatic cancer is the fourth-leading cause of cancer death in the U.S. Over 80% of patients present with incurable disease, and the vast majority live for <12 months. The high mortality of pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is largely a consequence of diagnosis at an advanced stage when the tumor is no longer resectable for cure. However, symptoms rarely develop with early disease, and established risk factors for PDAC, such as tobacco smoking, obesity, chronic pancreatitis, diabetes, and family history of PDAC, are insufficient to risk stratify the population for disease screening. Experimental studies indicate that more than a decade elapses from formation of the founder malignant clone to a patient's diagnosis, suggesting a window of opportunity for early detection. Nevertheless, no early detection markers have advanced to clinical use, in part, because little infrastructure has been developed to facilitate rigorous investigation of promising candidates. To address the critical goal of PDAC early detection, we have brought together investigators with a long track-record of collaborative innovation to form the Pancreatic Cancer Circulating Biomarker (Pan-C2-Bio) Consortium. Within this Consortium, we join ongoing patient biospecimen collection at five large cancer centers with four highly promising early detection technologies and sophisticated computer modeling to define a non-invasive PDAC screening strategy. The Consortium will work to achieve three primary goals: (1) generation of a large, unified, thoroughly-annotated human and murine sample bank for testing of early detection markers, (2) definitive evaluation of four highly promising PDAC early detection markers for near-term clinical utility, including circulating cell-free DNA mutations and methylation patterns, cancer-derived exosomes, and metabolism markers, and (3) identification of biomarker-based screening strategies to facilitate early cancer diagnosis in high-risk groups and the general population. Thus, the work proposed by the Pan-C2-Bio Consortium will deliver much-needed biospecimen resources for early detection studies, provide evidence for (or against) the utility of four highly promising PDAC early detection technologies, and demonstrate how new biomarkers can be integrated with previously characterized risk factors to identify individuals for disease screening. With this work, we look to reduce mortality from pancreatic cancer by identifying those at highest risk and diagnosing subclinical disease when curative therapies can be applied.

Public Health Relevance

(2-3 sentences, relevance to public health): Pancreatic cancer is a major cause of cancer death in the United States, due largely to its late stage at diagnosis. We join together five large cancer centers with a track-record of innovation and collaboration to accomplish three primary goals: (1) generate thoroughly-annotated human and murine sample banks for testing of early detection markers, (2) rigorously evaluate highly promising early detection markers for near- term clinical utility, including circulating cell-free DNA, exosomes, and metabolism markers, and (3) construct risk stratification models to integrate early detection markers into screening programs for high-risk groups and the general population. Thus, the goal of this proposal to is reduce pancreatic cancer mortality by diagnosing the cancer when it is still at an early stage and amenable to curative treatments.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA210171-03
Application #
9517774
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Rinaudo, Jo Ann S
Project Start
2016-07-15
Project End
2021-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
Danai, Laura V; Babic, Ana; Rosenthal, Michael H et al. (2018) Altered exocrine function can drive adipose wasting in early pancreatic cancer. Nature 558:600-604
Fujisaka, Shiho; Avila-Pacheco, Julian; Soto, Marion et al. (2018) Diet, Genetics, and the Gut Microbiome Drive Dynamic Changes in Plasma Metabolites. Cell Rep 22:3072-3086
Klein, Alison P; Wolpin, Brian M; Risch, Harvey A et al. (2018) Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. Nat Commun 9:556
Khalaf, Natalia; Yuan, Chen; Hamada, Tsuyoshi et al. (2018) Regular Use of Aspirin or Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs Is Not Associated With Risk of Incident Pancreatic Cancer in Two Large Cohort Studies. Gastroenterology 154:1380-1390.e5
Hamada, Tsuyoshi; Khalaf, Natalia; Yuan, Chen et al. (2018) Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer. Clin Gastroenterol Hepatol 16:1300-1306.e3
Qian, Zhi Rong; Rubinson, Douglas A; Nowak, Jonathan A et al. (2018) Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma. JAMA Oncol 4:e173420
Aguirre, Andrew J; Nowak, Jonathan A; Camarda, Nicholas D et al. (2018) Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine. Cancer Discov 8:1096-1111
Guibert, N; Hu, Y; Feeney, N et al. (2018) Amplicon-based next-generation sequencing of plasma cell-free DNA for detection of driver and resistance mutations in advanced non-small cell lung cancer. Ann Oncol 29:1049-1055
Ulrich, Bryan C; Paweletz, Cloud P (2018) Cell-Free DNA in Oncology: Gearing up for Clinic. Ann Lab Med 38:1-8
Hu, Yuebi; Ulrich, Bryan; Supplee, Julianna et al. (2018) False positive plasma genotyping due to clonal hematopoiesis. Clin Cancer Res :

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