– In xenograft models, RNA seq analysis following adagrasib showed that MAPK pathway negative regulators were the most strongly decreased genes.– In xenografts, magnitude of reduction of MYC and cyclin B1 protein levels correlated with adagrasib anti-tumor activity. – In H2122 xenografts, CRISPR/Cas9 screen revealed that sgRNA targeting cell cycle, SHP2, MYC and mTOR were the top depleted sgRNA on adagrasib treatment. sgRNA targeting KEAP1 were enriched in H2122 xenograft models treated with adagrasib. This evidence concerns the gene CCNB1 and neoplasm.