The pathogenesis of hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most common and deadly malignancies worldwide. The multikinase inhibitor sorafenib still remains the only approved agent for advanced HCC. In most cases, HCC develops based on advanced liver cirrhosis, whereas the underlying risk factors can be identified in the vast majority of patients. Methods: Here, we summarise and review the pathomechanisms in dependence of the underlying disease, gene signatures and frequent mutations in HCC. Results: Worldwide, HCC is most commonly caused by viral hepatitis B and C. It is less frequently associated with chronic exposure to toxins or hereditary liver diseases. Non-alcoholic fatty liver disease is an emerging risk factor with increasing prevalence nowadays. Emerging innovative technologies including whole-genome or -exome analyses have been applied for molecular and prognostic classifications as well as therapeutic implications. Mutations leading to activation of the Wnt pathway and inactivation of p53 were most frequently identified in HCC. Conclusions: Recent advances have significantly improved our understanding of the molecular pathogenesis of HCC and its complex genetic landscape. The emerging data will open the door towards novel and more effective targeted and personalized therapies in this devastating disease.