RTK activation along with frequent loss of the cell cycle tumor suppressor CDKN2A in chordomas (24, 38, 57, 58) has motivated preclinical repurposing studies with CDK4/6 inhibitors (39, 59, 60) and a Phase II trial involving palbociclib in CDKN2A-null chordoma patients (NCT03110744). The gene discussed is CDK4; the disease is chordoma.