However, in tumors without proficient RB CDK4/6 inhibition is not effective.26 Furthermore, TP53 mutations appeared to be strongly related to CDK4/6 inhibitor resistance in a panel of 560 cancer cell lines treated with palbociclib and abemaciclib.27 This is in line with our findings and could explain the worse PFS observed in the TP53 mutated cases. The gene discussed is TP53; the disease is cancer.