Inhibiting TGF-β signaling in hepatocellular carcinoma

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 t...

Full description

Saved in:
Bibliographic Details
Published in:Biochimica et biophysica acta 2011-04, Vol.1815 (2), p.214-223
Main Authors: Giannelli, Gianluigi, Mazzocca, Antonio, Fransvea, Emilia, Lahn, Michael, Antonaci, Salvatore
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - therapeutic use
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - metabolism
Hepatocellular carcinoma
Humans
Liver Neoplasms - drug therapy
Liver Neoplasms - metabolism
Signal Transduction - drug effects
Small molecule inhibitors of TGF-β receptor kinase
Stromal-tumor interactions
Target-based therapies
Transforming Growth Factor beta - antagonists & inhibitors
Transforming Growth Factor beta - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0304-419X
0006-3002
1879-2561
DOI:10.1016/j.bbcan.2010.11.004