Inhibiting TGF-β signaling in hepatocellular carcinoma.

Abstract

One of the main complications in patients with liver fibrosis is the development of hepatocellular carcinoma (HCC). An understanding of the molecular mechanisms leading to HCC is important in order to be able to design new pharmacological agents serving either to prevent or mitigate the outcome of this malignancy. The transforming growth factor-beta (TGF-β) cytokine and its isoforms initiate a signaling cascade which is closely linked to liver fibrosis, cirrhosis and subsequent progression to HCC. Because of its role in these stages of disease progression, TGF-β appears to play a unique role in the molecular pathogenesis of HCC. Thus, it is a promising target for pharmacological treatment strategies. Recent studies have shown that inhibition of TGF-β signaling results in multiple synergistic down-stream effects which will likely improve the clinical outcome in HCC. We also review a number of TGF-β inhibitors, most of which are still in a preclinical stage of development, but may soon be available for trial in HCC patients. Hence, it is anticipated that there will soon be new agents available for clinical investigations to evaluate the role of the TGF-β-associated signaling in this deadly cancer.

• Authors: Gianluigi Giannelli, Antonio Mazzocca, Emilia Fransvea, Michael Lahn, Salvatore Antonaci
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1815 Issue 2 Pg. 214-23 (Apr 2011) ISSN: 0006-3002 [Print] Netherlands
• PMID: 21129443 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Transforming Growth Factor beta

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, metabolism)
• Humans
• Liver Neoplasms (drug therapy, metabolism)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta (antagonists & inhibitors, metabolism)