RAFi-induced activation of ERK1/2 can be mitigated by combination with a MEKi such as Trametinib; this combination enhances ERK1/2 inhibition in BRAFV600E/K tumour cells but antagonises paradoxical ERK1/2 activation in tissue that lacks BRAF mutations, thereby providing a large, BRAFV600E/K tumour-selective therapeutic window3,4. Here, MAPK3 is linked to neoplasm.