Stable reconstitution of DUSP6/MKP-3 restored both sensitivity to crizotinib and the ability of this drug to supress ERK signalling while shRNA-mediated knockdown of DUSP6/MKP-3 promoted crizotinib resistance in parental ELM4–ALK lung adenocarcinoma cells and this was accompanied by rescue of ERK activation. Here, ALK is linked to lung adenocarcinoma.