CDKN2A and chordoma: ,16 It is approved for the treatment of breast cancer in combination with endocrine therapy and has also been studied in CDK4-amplified liposarcomas17,18 and other solid tumors with deregulation of the CDK4/6-RB axis.19, 20, 21, 22 Consistent with the hypothesis that CDK4/6 may be therapeutic targets in chordoma, palbociclib inhibits the proliferation of p16-deficient chordoma cell lines, and a molecular signature predicting sensitivity to CDK4/6 blockade has been proposed that includes p16 loss and expression of CDK4/6 and phosphorylated RB1 (S780).13