Feldmann Georg, Rauenzahn Sherri, Maitra Anirban
Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Expert Opin Drug Discov. 2009 Apr 1;4(4):429-443. doi: 10.1517/17460440902821657.
Pancreatic cancer is a disease of near uniform fatality and the overwhelming majority of patients succumb to their advanced malignancy within a few months of diagnosis. Despite considerable advances in our understanding of molecular mechanisms underlying pancreatic carcinogenesis, this knowledge has not yet been fully translated into clinically available treatment strategies that yield significant improvements in disease free or overall survival. OBJECTIVE: Cell line-based in vitro model systems provide powerful tools to identify potential molecular targets for therapeutic intervention as well as for initial pre-clinical evaluation of novel drug candidates. Here we provide a brief overview of recent literature on cell line-based model systems of pancreatic cancer and their application in the search for novel therapeutics against this vicious disease. CONCLUSION: While in vitro models of pancreatic cancer are of tremendous value for genetic studies and initial functional screenings in drug discovery, they carry several imanent drawbacks and are often poor in predicting therapeutic response in humans. Therefore, in most instances they are successfully exploited to generate hypothesis and identify molecular targets for novel therapeutics, which are subsequently subject to further in-depth characterization using more advanced in vivo model systems and clinical trials.
胰腺癌是一种几乎必死无疑的疾病，绝大多数患者在确诊后的几个月内就会因晚期恶性肿瘤而死亡。尽管我们对胰腺癌发生的分子机制有了相当大的进展，但这些知识尚未完全转化为临床上可用的治疗策略，从而在无病生存期或总生存期方面产生显著改善。目的：基于细胞系的体外模型系统为识别治疗干预的潜在分子靶点以及对新型候选药物进行初步临床前评估提供了强大工具。在此，我们简要概述了近期关于基于细胞系的胰腺癌模型系统及其在寻找针对这种恶性疾病的新型疗法中的应用的文献。结论：虽然胰腺癌的体外模型在基因研究和药物发现的初始功能筛选中具有巨大价值，但它们存在一些内在缺点，并且在预测人类治疗反应方面往往较差。因此，在大多数情况下，它们被成功用于产生假设并识别新型疗法的分子靶点，随后使用更先进的体内模型系统和临床试验对这些靶点进行进一步深入研究。
