Saiki Yuriko, Jiang Can, Ohmuraya Masaki, Furukawa Toru
Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Department of Genetics, Hyogo College of Medicine, Hyogo 663-8501, Japan.
Cancers (Basel). 2021 Dec 24;14(1):71. doi: 10.3390/cancers14010071.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, and the seventh leading cause of cancer-related deaths worldwide. An improved understanding of tumor biology and novel therapeutic discoveries are needed to improve overall survival. Recent multi-gene analysis approaches such as next-generation sequencing have provided useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic cancer and precursor lesions are characterized by specific molecular alterations. Genetically engineered mouse models (GEMMs) of PDAC are useful to understand the roles of altered genes. Most GEMMs are driven by oncogenic Kras, and can recapitulate the histological and molecular hallmarks of human PDAC and comparable precursor lesions. Advanced GEMMs permit the temporally and spatially controlled manipulation of multiple target genes using a dual-recombinase system or CRISPR/Cas9 gene editing. GEMMs that express fluorescent proteins allow cell lineage tracing to follow tumor growth and metastasis to understand the contribution of different cell types in cancer progression. GEMMs are widely used for therapeutic optimization. In this review, we summarize the main molecular alterations found in pancreatic neoplasms, developed GEMMs, and the contribution of GEMMs to the current understanding of PDAC pathobiology. Furthermore, we attempted to modify the categorization of altered driver genes according to the most updated findings.
胰腺导管腺癌（PDAC）是一种极具侵袭性的恶性肿瘤，是全球癌症相关死亡的第七大主要原因。需要更好地了解肿瘤生物学并发现新的治疗方法以提高总体生存率。最近的多基因分析方法，如下一代测序，为胰腺肿瘤的分子特征提供了有用信息。不同类型的胰腺癌和癌前病变具有特定的分子改变特征。PDAC的基因工程小鼠模型（GEMMs）有助于理解基因改变的作用。大多数GEMMs由致癌性Kras驱动，能够重现人类PDAC及类似癌前病变的组织学和分子特征。先进的GEMMs允许使用双重组酶系统或CRISPR/Cas9基因编辑对多个靶基因进行时空控制操作。表达荧光蛋白的GEMMs能够进行细胞谱系追踪，以跟踪肿瘤生长和转移，从而了解不同细胞类型在癌症进展中的作用。GEMMs被广泛用于治疗优化。在本综述中，我们总结了胰腺肿瘤中发现的主要分子改变、已开发的GEMMs，以及GEMMs对当前理解PDAC病理生物学的贡献。此外，我们尝试根据最新发现对改变的驱动基因分类进行修改。
