Treatment of hepatocellular carcinoma: considerations regarding etiology and molecular biology.

Advanced and metastatic hepatocellular carcinomas (HCC) are challenging to treat, and no cytotoxic agents have thus far improved survival. The underlying liver cirrhosis that commonly accompanies HCC provides an additional challenge; indeed, functional scoring of the cirrhosis and the cancer is a critical component of patient evaluation. The molecular biology and pathogenesis of HCC are being actively investigated, which may lead to better understanding of the evolution of the disease, especially differing etiologies and identification of survival genes that may affect outcome. Early studies of targeted therapies in HCC have shown disease stabilizations, and increased understanding of the mechanisms of these novel agents combined with correlative studies may lead to the identification of an active agent or combination of agents that improves the natural history of HCC. Recently, a randomized phase III study of sorafenib vs. placebo showed a statistically and clinically significant improvement in survival, which will most likely establish sorafenib as the new standard of care of systemic therapy for advanced HCC.