家族性胰腺癌研究：弥合基础研究与临床应用之间的差距。
Familial Pancreatic Cancer Research: Bridging Gaps in Basic Research and Clinical Application.
机构信息
Department of Microbiology and Molecular Genetics, College of Biological Sciences, University of California, Davis, Davis, CA 95616, USA.
University of California Davis Comprehensive Cancer Center, University of California, Davis, Sacramento, CA 95817, USA.
出版信息
Biomolecules. 2024 Oct 30;14(11):1381. doi: 10.3390/biom14111381.
Familial pancreatic cancer (FPC) represents a significant yet underexplored area in pancreatic cancer research. Basic research efforts are notably limited, and when present, they are predominantly centered on the and mutations due to the scarcity of other genetic variants associated with FPC, leading to a limited understanding of the broader genetic landscape of FPC. This review examines the current state of FPC research, focusing on the molecular mechanisms driving pancreatic ductal adenocarcinoma (PDAC) progression. It highlights the role of homologous recombination (HR) and its therapeutic exploitation via synthetic lethality with PARP inhibitors in BRCA1/2-deficient tumors. The review discusses various pre-clinical models of FPC, including conventional two-dimensional (2D) cell lines, patient-derived organoids (PDOs), patient-derived xenografts (PDXs), and genetically engineered mouse models (GEMMs), as well as new advancements in FPC research.
家族性胰腺癌（FPC）是胰腺癌研究中一个重要但尚未得到充分探索的领域。基础研究工作明显有限，而且当存在时，它们主要集中在 和 突变上，因为与 FPC 相关的其他遗传变异较少，导致对 FPC 更广泛的遗传图谱的理解有限。这篇综述检查了 FPC 研究的现状，重点是驱动胰腺导管腺癌（PDAC）进展的分子机制。它强调了同源重组（HR）的作用及其通过与 PARP 抑制剂的合成致死性在 BRCA1/2 缺陷肿瘤中的治疗利用。该综述讨论了 FPC 的各种临床前模型，包括传统的二维（2D）细胞系、患者来源的类器官（PDO）、患者来源的异种移植物（PDX）和基因工程小鼠模型（GEMM），以及 FPC 研究的新进展。
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