[Molecular pathogenesis of hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. HCC nearly almost always develops in connection with chronic hepatitis or liver cirrhosis, mainly due to hepatitis B virus or hepatitis C virus infection. Several factors are supposed to play key roles in the development of HCC, such as aberrant viral protein expression, genomic instability with/without insertions of viral DNAs, gene mutations, epigenetic gene modification, oxidative stress, and alteration of the microenvironment including inflammation, fibrosis, and emergence of stem/progenitor cells as a result of repeated necrosis and regeneration of hepatocytes. The elucidation of molecular mechanisms of hepatocarcinogenesis has successfully provided small molecule inhibitors targeting aberrantly activated signaling in HCC. Development of novel classification systems based on the molecular profiles and drug sensitivities against molecularly targeted compounds is currently underway to facilitate novel strategies for effective eradication of HCC.