Overall, our findings indicate that in the context of KRASMUT CRC Palbo-resistance could be overcome by the concomitant use of Src inhibitors and that evaluation of p27 expression in tumor tissue might be sufficient to select KRASMUT CRC patients who may benefit from administration of CDK4/6 inhibitors, alone or in combination with Src inhibitors. This evidence concerns the gene CDK4 and colorectal carcinoma.