To investigate the contribution of Smad4 LOF in lung cancer progression and metastasis in the context of conditional mouse lung cancer models, we utilized existing Cre/LoxP–controlled, genetically engineered mouse models with Kras (KrasG12D)14, p53 LOF (p53fl/fl)15, and Smad4 LOF (Smad4fl/fl)24,25 mutations to generate a cohort of lung tumors by nasal delivery of an adenovirus expressing Cre recombinase (adeno-Cre). Here, SMAD4 is linked to lung cancer.