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Early neoplastic lesions of the pancreas: initiation, progression, and opportunities for precancer interception
Brian A. Pedro, Laura D. Wood
Brian A. Pedro, Laura D. Wood
Published July 15, 2025
Citation Information: J Clin Invest. 2025;135(14):e191937. https://doi.org/10.1172/JCI191937.
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Review Series

Early neoplastic lesions of the pancreas: initiation, progression, and opportunities for precancer interception

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is known to progress from one of two main precursor lesions: pancreatic intraepithelial neoplasia (PanIN) or intraductal papillary mucinous neoplasm (IPMN). The poor survival rates for patients with PDAC, even those diagnosed with localized disease, highlight the need for pancreatic cancer interception at the precursor stage. Although their basic biological drivers are well characterized, practical strategies for PanIN and IPMN interception remain elusive due to difficulties with detection, risk stratification, and low-morbidity intervention. Recently, advances in liquid biopsy, spatial multiomics analysis, and machine learning technology have provided deeper understanding of the molecular landscapes underlying pancreatic precursor development and progression. In this Review, we outline the different histologic phenotypes, clinical characteristics, and neoplastic cell–intrinsic and –extrinsic drivers of PanINs and IPMNs, with particular focus on current and potential future opportunities for pancreatic precancer interception.

Authors

Brian A. Pedro, Laura D. Wood

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Figure 3

Current and potential opportunities for pancreatic precancer interception.

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Current and potential opportunities for pancreatic precancer interceptio...
Schematic of current and theoretical strategies for PanIN and IPMN interception, categorized by lesion type and role in interception (diagnosis or intervention). PanIN detection strategies are limited but include certain imaging features and pancreatic juice analysis. Current IPMN detection strategies include imaging and cyst fluid analysis, with multiple composite biomarkers for risk stratification recently becoming available. Liquid biopsy analysis of peripheral blood has not been thoroughly studied for precursor lesions but is theoretically applicable. Potential intervention strategies for both PanINs and IPMNs include surgical resection, immune-based therapies, or KRAS-targeted therapies.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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