Loss of the protein tyrosine phosphatases PTPN1 and PTPN2 promote ALK-dependent phosphorylation and activation of STAT3 and SHP2, both of which promote resistance to crizotinib in ALK⁺ ALCL. Consequently, as demonstrated by Karaca-Ataby et al, allosteric SHP2 inhibitors may be rationally combined with crizotinib in ALK⁺ ALCL. Professional illustration by Somersault 18:24.