文章：

胰腺癌的进化和异质性：整合组学和临床数据

Pancreatic cancer evolution and heterogeneity: integrating omics and clinical data

原文发布日期：2021-11-17

DOI: 10.1038/s41568-021-00418-1

类型: Review Article

开放获取: 否

英文摘要：

Pancreatic ductal adenocarcinoma (PDAC), already among the deadliest epithelial malignancies, is rising in both incidence and contribution to overall cancer deaths. Decades of research have improved our understanding of PDAC carcinogenesis, including characterizing germline predisposition, the cell of origin, precursor lesions, the sequence of genetic alterations, including simple and structural alterations, transcriptional changes and subtypes, tumour heterogeneity, metastatic progression and the tumour microenvironment. These fundamental advances inform contemporary translational efforts in primary prevention, screening and early detection, multidisciplinary management and survivorship, as prospective clinical trials begin to adopt molecular-based selection criteria to guide targeted therapies. Genomic and transcriptomic data on PDAC were also included in the international pan-cancer analysis of approximately 2,600 cancers, a milestone in cancer research that allows further insight through comparison with other tumour types. Thus, this is an ideal time to review our current knowledge of PDAC evolution and heterogeneity, gained from the study of preclinical models and patient biospecimens, and to propose a model of PDAC evolution that takes into consideration findings from varied sources, with a particular focus on the genomics of human PDAC.

摘要翻译： 

胰腺导管腺癌（PDAC）是目前致死率最高的上皮性恶性肿瘤之一，其发病率和在癌症总死亡中的贡献率均呈上升趋势。数十年来的研究增进了我们对PDAC致癌机制的理解，包括种系易感性、起源细胞、前驱病变的鉴定，基因改变（包括简单变异和结构变异）的顺序，转录变化与分子亚型，肿瘤异质性，转移进程以及肿瘤微环境。这些基础性进展为当前转化研究提供了方向，涉及一级预防、筛查与早期检测、多学科诊疗和生存管理——随着前瞻性临床试验开始采用分子分型标准指导靶向治疗。PDAC的基因组和转录组数据已被纳入涵盖约2600种癌症的国际泛癌种分析项目，这一癌症研究的里程碑使得通过与其他肿瘤类型比较获得更深层次认知成为可能。因此，此刻正是审视我们通过临床前模型和患者生物样本研究获得的PDAC进化与异质性知识的理想时机，并提出一个整合多源研究发现（特别聚焦于人类PDAC基因组学）的PDAC进化模型。

原文链接：

Pancreatic cancer evolution and heterogeneity: integrating omics and clinical data