RAF1 and metastatic melanoma: Moreover, the intensive efforts to develop inhibitors of RAS post-translational modifications such as FTase inhibitors have failed in the past due to compensatory activity of the geranyl modifications.34, 35 In contrast, clinical studies have demonstrated improved efficacy by inhibiting the RAS effector signalling pathways and the next generation of RAF, MEK and ERK inhibitors have entered clinical trials demonstrating promising clinical activity in metastatic melanoma and other tumour types.