MAPK3 and neoplasm: Whilst future studies should aim to define how ER stress impairs ERK1/2 signalling, our results indicate that ERK1/2 signalling is a key determinant of ER stress-induced apoptosis based on three key observations: (i) activation of ERK1/2 by ΔCRAF:ER protected cells from apoptosis; (ii) the MEK1/2 inhibitor selumetinib or the ERK1/2 inhibitor SCH772984 enhanced apoptosis induced by ER stress in fibroblasts and (iii) tumour cells with BRAFV600E exhibited constitutive ERK1/2 signalling and MEK1/2-dependent resistance to ER stress.