Pedro Brian A, Wood Laura D
Department of Pathology, and.
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Clin Invest. 2025 Jul 15;135(14). doi: 10.1172/JCI191937.
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.
胰腺导管腺癌（PDAC）已知由两种主要的前驱病变之一发展而来：胰腺上皮内瘤变（PanIN）或导管内乳头状黏液性肿瘤（IPMN）。PDAC患者的生存率很低，即使是那些被诊断为局限性疾病的患者，这凸显了在前驱阶段进行胰腺癌拦截的必要性。尽管它们的基本生物学驱动因素已得到充分表征，但由于检测、风险分层和低发病率干预方面的困难，PanIN和IPMN拦截的实际策略仍然难以捉摸。最近，液体活检、空间多组学分析和机器学习技术的进展使人们对胰腺前驱病变发展和进展的分子格局有了更深入的了解。在本综述中，我们概述了PanIN和IPMN的不同组织学表型、临床特征以及肿瘤细胞内在和外在驱动因素，特别关注当前和未来胰腺癌癌前病变拦截的机会。
