In this study, we therefore focused our pharmacological expertise on the CDK4/6 inhibitor palbociclib and the PLK1-inhibitor volasertib in two xenograft models harboring homozygous deletions of CDKN2A/2B, and in a third PBRM1-mutated model (control), in order to evaluate the CDKN2A/2B loss as a theranostic biomarker in chordomas. The gene discussed is CDKN2A; the disease is chordoma.