Dysregulation of Signaling Pathways Plays a Role in the Development and Pathogenesis of Hepatocellular Carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is the fifth most common solid malignancy worldwide and causes more than 600,000 deaths annually. Many risk factors predispose to HCC, these risk factors may present individually or collectively depending on the environmental situations. The risk factors for HCC include hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholism, aflatoxin (AF), schistosomiasis and some hereditary diseases as haemochromatosis and haemophilia. Certain key regulatory signaling pathways integrated in the pathogenesis of HCC such as insulin-like growth factor (IGF) signaling pathway, transforming growth factor-β (TGF-β) signaling pathway, Toll-like receptor (TLR) signaling pathway and Notch signaling pathway. Dysregulation of different signaling pathways at any level including the receptors and downstream signaling pathway components represent a central protumorigenic principle in human hepatocarcinogenesis and this dysregulation can be targeted for new therapeutic modalities for HCC. Aim of the Work: The aim of the present work was to study the recently discussed signaling pathways integrated in development of hepatocellular carcinoma in the high risk groups, and how genetic alterations in theses signaling pathways is a potentiating factor for HCC from the year 2000 until now. New diagnostic and therapeutic modalities for that disease could be provided by targeting these dysregulated signaling pathways. Conclusion: Finally, it could be concluded that: 1) There are multiple mechanisms underlying the hepatocarcinogenesis and by these mechanisms, early diagnosis for HCC could be possible.  2) Understanding the signaling pathways dysregulated in high risk groups for HCC may provide new diagnostic and therapeutic modalities.