Deregulation of their expression by various mechanisms (e.g., promoter methylation, point mutations, post-translational mechanisms) may result in Ras/Raf/MEK/ERK pathway activation in the absence of detectable mutations at either Raf or MEK. Hence, the Ras/Raf/MEK/ERK cascade is a therapeutic target in HCC [3, 95, 96]. The gene discussed is MAPK1; the disease is hepatocellular carcinoma.