CDK4 and chordoma: EGFR-inhibitor and CDK4/6-inhibitor sensitivity in chordoma has been described previously20,21; thus, we focused on inhibitors of Src homology-2 domain-containing phosphatase 2 (SHP2), the protein encoded by PTPN11. SHP2 is a tyrosine phosphatase that promotes signal transduction downstream of receptor tyrosine kinases to activate the RAS/mitogen-activated protein kinase (MAPK) cascade, and has additional functions in modulating tumor immunity33; the recent development of selective, allosteric compounds targeting SHP2 led us to investigate their therapeutic potential in chordoma45–48.