Hepatocellular carcinoma: molecular biology and therapy

Abstract

Advanced and metastatic hepatocellular carcinomas (HCC) are challenging to treat, and no cytotoxic agents have impacted survival. The underlying liver cirrhosis that commonly accompanies HCC provides an additional challenge; indeed, functional scoring of cirrhosis and HCC is a critical component of patient evaluation. Currently, the molecular biology and pathogenesis of HCC are being increasingly 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 stabilization, and an increased understanding of the mechanism(s) of these novel agents combined with correlative studies may lead to the identification of an active agent or combination of agents that impacts the natural history of HCC.

Figure 1

Survival as a function of CLIP score. Abbreviations: CLIP, The Cancer of the Liver Italian Program.

Figure 2

Survival as a function of CUPI score. Abbreviations: CUPI, Chinese University Prognostic Index.

Figure 3

Macro and micro evolution of HCC. Abbreviations: HCC, hepatocellular carcinoma; IGF, liver-derived insulin-like growth factor; TGF, transforming growth factor; Raf, rat sarcoma virus oncogene activated factor.

Figure 4

Sequential apoptotic activation. Flavopiridol was given 7 hours after SN38, the active metabolite of irinotecan, resulting in cleavage of the Poly (ADP-ribose) polymerase (PARP) and caspase-3 activation.