MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

SIMPLE SUMMARY: The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway is frequently activated in liver cancer, which is one of the most lethal cancers in humans. In addition to genetic mutation leading to persistent activation of effector molecules in the MAPK/ERK signaling cascade, there are alternative means by which the MAPK/ERK signaling pathway is activated in cancer. In this review, we will introduce the diverse modulators regulating the MAPK/ERK signaling pathway and consider the possibility of targeting the effectors and regulators in order to suppress the pro-tumorigenic MAPK/ERK signaling pathway, especially in liver cancer. ABSTRACT: Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence is increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic and clinical researchers. The MAPK/ERK signaling pathway is activated in more than 50% of human HCC cases; however, activating mutations in RAS and RAF genes are rarely found in HCC, which are major genetic events leading to the activation of the MAPK/ERK signaling pathway in other cancers. This suggests that there is an alternative mechanism behind the activation of the signaling pathway in HCC. Here, we will review recent advances in understanding the cellular and molecular mechanisms involved in the activation of the MAPK/ERK signaling pathway and discuss potential therapeutic strategies targeting the signaling pathway in the context of HCC.