MAPK3 and neoplasm: Unfortunately, the approach to specifically target ERK1/2 MAPK signalling—even with combination therapy—is not completely effective, since the relief of ERK1/2 feedback by Raf or MEK1/2 inhibition also reduces the inhibition of parallel pathways that can promote survival and reduce the dependency of the tumour on ERK1/2 signalling (Fig. 3).