Cell cycle inhibitors such as abemaciclib and ribociclib, which impair cell cycle progression, target convergent nodes of the RAS-MAPK and PI3K-AKT pathways and provide a potential combination strategy to synergize with KRAS inhibitors.280 Preclinical models, both in vitro and in vivo, have suggested a synergistic benefit from the coinhibition of CDK4/6 and KRASG12C in both NSCLC and PDAC.281 This concept was clinically tested in CodeBreak 101 by combining sotorasib and palbociclib (NCT04185883). This evidence concerns the gene KRAS and non-small cell lung carcinoma.