Dennaoui Rayane, Shrestha Hridaya, Wagner Kay-Uwe
Department of Oncology, Wayne State University School of Medicine and Tumor Biology Program, Barbara Ann Karmanos Cancer Institute, 4100 John R, EL01TM, Detroit, MI, 48201, USA.
Cancer Metastasis Rev. 2021 Sep;40(3):803-818. doi: 10.1007/s10555-021-09989-9. Epub 2021 Sep 7.
Although pancreatic cancer remains to be a leading cause of cancer-related deaths in many industrialized countries, there have been major advances in research over the past two decades that provided a detailed insight into the molecular and developmental processes that govern the genesis of this highly malignant tumor type. There is a continuous need for the development and analysis of preclinical and genetically engineered pancreatic cancer models to study the biological significance of new molecular targets that are identified using various genome-wide approaches and to better understand the mechanisms by which they contribute to pancreatic cancer onset and progression. Following an introduction into the etiology of pancreatic cancer, the molecular subtypes, and key signaling pathways, this review provides an overview of the broad spectrum of models for pancreatic cancer research. In addition to conventional and patient-derived xenografting, this review highlights major milestones in the development of chemical carcinogen-induced and genetically engineered animal models to study pancreatic cancer. Particular emphasis was placed on selected research findings of ligand-controlled tumor models and current efforts to develop genetically engineered strains to gain insight into the biological functions of genes at defined developmental stages during cancer initiation and metastatic progression.
尽管在许多工业化国家,胰腺癌仍是癌症相关死亡的主要原因之一,但在过去二十年里,研究取得了重大进展,对控制这种高度恶性肿瘤类型发生的分子和发育过程有了详细的了解。持续需要开发和分析临床前和基因工程胰腺癌模型,以研究使用各种全基因组方法鉴定出的新分子靶点的生物学意义,并更好地理解它们促成胰腺癌发生和进展的机制。在介绍胰腺癌的病因、分子亚型和关键信号通路之后,本综述概述了用于胰腺癌研究的广泛模型。除了传统的和患者来源的异种移植外,本综述还重点介绍了化学致癌物诱导和基因工程动物模型开发中研究胰腺癌的主要里程碑。特别强调了配体控制肿瘤模型的选定研究结果,以及目前开发基因工程菌株以深入了解癌症起始和转移进展过程中特定发育阶段基因生物学功能的努力。