MAPK3 and keratoacanthoma: Unfortunately, since Raf inhibition in normal cells expressing wild-type Raf proteins activates the ERK1/2 pathway due to relief of negative feedback and the increased formation and activation of Raf dimers, treatment with these compounds can cause ectopic ERK1/2 signalling, with cutaneous lesions (squamous cell carcinoma and/or keratoacanthoma) among the most common problems [110, 111].