Understanding the early evolution of cancer heterogeneity during the initial steps of
tumorigenesis can uncover vulnerabilities of cancer cells that may be masked at later
stages. We describe a comprehensive approach employing gene expression analysis in
early lesions to identify novel therapeutic targets and the use of mouse models to test
synthetic lethal drug combinations to treat human Kirsten rat sarcoma viral oncogene
homologue (KRAS)-driven lung adenocarcinoma.