Molecular pathogenesis of human hepatocellular carcinoma

Abstract

Publisher Summary Hepatocellular carcinoma (HCC) is one of the most frequent human cancers. This chapter focuses on the compilation of molecular and functional changes identified in human HCCs and their interrelation and impact on tumor formation and therapy. The chapter explores the experimental data obtained in animal models, such as transgenic mouse lines, chemical rodent hepatocarcinogenesis, and models of virus-induced liver cancer. Human hepatocarcinogenesis usually develops on the histological background of a chronic liver disease, such as chronic hepatitis, chronic alcoholic liver disease, and hemochromatosis. The biology and prognosis of hepatocellular carcinoma significantly correlates with tumor stage and grade, but currently there is no evidence that tumor behavior is predictable from the macroscopic growth pattern, microscopic subtype, or any of the available immuno-histological markers. Only fibrolamellar HCC that is a rare, stroma-rich, oncocytic variant occurring predominantly in younger patients seems to have a better prognosis. Interference with growth factor signaling pathways by small molecules is an attractive therapeutic scheme with potential application in HCCs. All therapeutic approaches have to respect that in the majority of HCC patients, the surrounding liver is severely damaged, often showing complete cirrhosis. This imposes restrictions on therapeutic intervention and is often life-limiting in a manner comparable to the HCC itself.