In this context, our work that demonstrates in KRASMUT CRC that low p27 expression identifies high-risk patients that could benefit from the use of CDK4/6i, while high p27 expression, coupled with tyrosine phosphorylation by Src, may lead to Palbo-resistance, could be of great help in defining the clinical treatment decision tree for these patients. The gene discussed is SRC; the disease is colorectal carcinoma.