II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, München 81675, Germany.
Gut. 2012 Oct;61(10):1488-500. doi: 10.1136/gutjnl-2011-300756. Epub 2011 Aug 26.
Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease despite tremendous scientific efforts. Numerous trials have failed to improve the outcome on this deadliest of all major cancers. Potential causes include a still insufficient understanding of key features of this cancer and imperfect preclinical models for identification of active agents and mechanisms of therapeutic responses and resistance. Modern genetically engineered mouse models of PDAC faithfully recapitulate the genetic and biological evolution of human PDAC, thereby providing a potentially powerful tool for addressing tumour biological issues as well as strategies for early detection and assessment of responses to therapeutic interventions. Here, the authors will discuss opportunities and challenges in the application of genetically engineered mouse models for translational approaches in pancreatic cancer and provide a non-exhaustive list of examples with already existing or future clinical relevance.
尽管在科学研究上投入巨大,胰腺导管腺癌(PDAC)仍然是一种毁灭性疾病。众多临床试验未能改善这种所有主要癌症中最致命癌症的预后。潜在原因包括对这种癌症关键特征的理解仍然不足,以及用于鉴定有效药物和治疗反应及耐药机制的临床前模型并不完美。PDAC 的现代基因工程小鼠模型忠实地再现了人类 PDAC 的遗传和生物学演变,从而为解决肿瘤生物学问题以及早期检测和评估治疗干预反应的策略提供了一种潜在的强大工具。在这里,作者将讨论在胰腺癌转化研究中应用基因工程小鼠模型的机会和挑战,并提供一个已经具有或未来具有临床相关性的例子的非详尽列表。