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.
Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.