Consequently, whilst inhibitors of MEK or ERK1/2 will disrupt downstream signalling, they will also prevent ERK1/2-mediated feedback phosphorylation of RAF, resulting in further RAF activation; this drives the rapid ‘rebound’ reactivation of ERK1/2 signalling that is observed in RAS-mutant tumour cells with wild type RAF proteins. The gene discussed is MAPK3; the disease is neoplasm.