Methodology of murine lung cancer mimics clinical lung adenocarcinoma progression and metastasis

Lung cancer is the leading cause of cancer-related deaths, of which adenocarcinoma is the most common subtype. Despite this, lung adenocarcinoma and its metastasis are poorly understood, due to difficulties in feasibly recapitulating disease progression and predicting clinical benefits of therapy. We outline a methodology to develop immunogenic orthotopic lung adenocarcinoma mouse models, by injecting cell-specific cre viruses into the lung of a genetically engineered mouse, which mirrors cancer progression defined by the International Association for the Study of Lung Cancer. Evaluation of different cre virus/concentrations models demonstrate remarkable consistency in cancer initiation and metastasis, allowing for high throughput, while showing differences in timing and severity, offering greater flexibility when selecting models. Histological and immune profiles reflect clinical observations suggesting similar mechanisms are recapitulated and preliminary data show resultant tumors to be responsive to clinical treatments. We present a clinically relevant, next-generation murine model for studying lung adenocarcinoma.