a Department of Internal Medicine 3 , University Hospital of Bonn , Bonn , Germany.
Expert Opin Drug Discov. 2019 Feb;14(2):127-142. doi: 10.1080/17460441.2019.1566319. Epub 2019 Jan 18.
Despite the introduction of novel therapeutic regimens for advanced stages of pancreatic cancer, long-term survival and overall outcome for patients are still very poor. Suitable small animal models are a prerequisite for better understanding of underlying pathophysiology and for translational studies designed to uncover novel therapeutic targets and to evaluate therapy regimens on a preclinical level. Areas covered: Genetically engineered mouse models as well as syngenic and xenotransplantation models are summarized and critically discussed with respect to their value for pancreatic cancer translational research. Expert opinion: Mouse models of pancreatic cancer represent a valuable tool for translational studies and are indispensable in order to develop novel potent drugs against pancreatic cancer. More complex genetically engineered mouse models are being developed to cover the complex genomic alterations found in human pancreatic cancers and to enable studies correlating genotype with response to specific therapeutic interventions. Another promising area of research in this field is the refinement and further development of humanized patient-derived xenograft models.
尽管针对胰腺癌晚期阶段引入了新的治疗方案,但患者的长期生存和总体预后仍然很差。合适的小动物模型是更好地了解潜在病理生理学和设计旨在发现新的治疗靶点以及在临床前水平评估治疗方案的转化研究的前提。
本文总结了基因工程小鼠模型以及同基因和异种移植模型,并就其在胰腺癌转化研究中的价值进行了批判性讨论。
胰腺癌的小鼠模型是转化研究的宝贵工具,对于开发针对胰腺癌的新型有效药物是不可或缺的。正在开发更复杂的基因工程小鼠模型,以覆盖人类胰腺癌中发现的复杂基因组改变,并能够进行将基因型与对特定治疗干预的反应相关联的研究。该领域另一个有前途的研究领域是改进和进一步开发人源化患者来源的异种移植模型。