Genetically Engineered Mouse Models of K-Ras-Driven Lung and Pancreatic Tumors: Validation of Therapeutic Targets
Genetically Engineered Mouse Models of K-Ras-Driven Lung and Pancreatic Tumors: Validation of Therapeutic Targets
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DOI：
10.1101/cshperspect.a031542
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发表时间：
2018-05-01
影响因子：
5.4
通讯作者：
Barbaci, Mariano
中科院分区：
文献类型：
--
作者：
Droste, Matthias;Guerr, Carmen;Barbaci, Mariano
K-RAS信号已经被深入研究了40多年。然而，到目前为止，还没有药物被批准用于治疗K-RAS突变型癌症。自世纪之交以来，科学家们使用基因工程小鼠（GEM）模型在实验室环境中复制K-RAS突变型癌症，以阐明导致这些肿瘤发生和进展的分子事件，并确定合适的治疗方法。在这篇综述中，我们概述了两种已知由K-RAS突变驱动的肿瘤类型的可用GEM模型的简要描述：肺腺癌和胰腺导管腺癌。此外，我们总结了一系列的研究，使用这些GEM肿瘤模型，以验证，无论是通过遗传学或药理学方法，各种目标的治疗潜力，最终目标是将这些结果转化为临床环境。
K-RAS signaling has been intensely studied for over 40 years. Yet, as of today, no drugs have been approved to treat K-RAS mutant cancers. Since the turn of the century, scientists have used genetically engineered mouse (GEM) models to reproduce K-RAS mutant cancers in a laboratory setting to elucidate those molecular events responsible for the onset and progression of these tumors and to identify suitable therapies. In this review, we outline a brief description of available GEM models for two tumor types known to be driven by K-RAS mutations: lung adenocarcinoma and pancreatic ductal adenocarcinoma. In addition, we summarize a series of studies that have used these GEM tumor models to validate, either by genetic or pharmacological approaches, the therapeutic potential of a variety of targets, with the ultimate goal of translating these results to the clinical setting.