Resistance to anti-cancer therapies evolves dynamically within 6–12 months of starting treatment due to various mechanisms, and combined drug treatment is a promising strategy for tackling resistance.5,7–9,11,21,22 In this study, we investigated the impact of combining Palbociclib (CDK 4/6 inhibitor), with either Gedatolisib (PI3K/mTOR dual inhibitor) or PD0325901 (selective MEK 1/2 inhibitor) on CRC cell line growth. This evidence concerns the gene MAP2K1 and colorectal carcinoma.