In May 2021, the FDA approved sotorasib (Lumakras™) as the first treatment for adult patients with non-small cell lung cancer (NSCLC) harboring the KRASG12C mutation. To study the relationship between this mutational activation of KRAS and tumorigenesis, and promote the development of KRASG12C inhibitors, we established a Cre-dependent KrasFLEX-G12C strain. In the presence of Cre, the oncogenic KRASG12C protein will be expressed at endogenous levels allowing for spatial and temporal control of tumorigenesis. In this study, KrasFLEX-G12C mice were crossed with the Sftpc-IRES-iCre mice which expresses Cre specifically in Type II alveolar cells to develop a spontaneous tumor model for lung cancer. These mice developed lung cancer at 14 weeks of age.
In conclusion, KrasFLEX-G12C mice can be used to study the occurrence and development of lung cancer when the oncogenic protein is expressed under the guidance of a lung-specific promoter. Such mice are also suitable for the preclinical research and development of cancer therapies.