Abstract
Hepatocellular carcinoma (HCC) is a cancer that usually develops on a liver already compromised by cirrhosis. Study of the underlying molecular mechanisms is essential so as to improve therapeutic strategies and to develop new pharmacological agents that may prevent or improve the course of this malignancy. Transforming growth factor-beta (TGF-β) intervenes in the process of hepatic fibrogenesis and cirrhosis, two pathogenic preconditions for the formation and progression of HCC [1] [2]. In addition, TGF-β plays a crucial role in the molecular pathogenesis of HCC and may, therefore, prove to be a promising drug target. We and other authors have recently demonstrated that inhibition of the TGF-β signaling pathway results in a synergistic downstream action with an inhibitory effect on the progression of HCC. Several TGF-β inhibitors have recently been developed, most of which are still in a preclinical phase, but they may soon be available for testing in patients with HCC. However, well-designed clinical trials will be needed to evaluate the effectiveness of these new agents prior to routine use in the clinic. Aim of this article is to make a brief review of the benefits and limitations of targeting the TGF-β signaling pathway in HCC.
Keywords: Hepatocellular carcinoma, inhibitors of the TGF-β kinase receptor, mechanism-based drugs, stroma-tumor interactions, cirrhosis, malignancy, TGF-β signaling pathway, clinical trials, drug, preclinical phase.
Current Pharmaceutical Design
Title:The TGF-β Signaling Pathway as a Pharmacological Target in a Hepatocellular Carcinoma
Volume: 18 Issue: 27
Author(s): Antonio Mazzocca, Salvatore Antonaci and Gianluigi Giannelli
Affiliation:
Keywords: Hepatocellular carcinoma, inhibitors of the TGF-β kinase receptor, mechanism-based drugs, stroma-tumor interactions, cirrhosis, malignancy, TGF-β signaling pathway, clinical trials, drug, preclinical phase.
Abstract: Hepatocellular carcinoma (HCC) is a cancer that usually develops on a liver already compromised by cirrhosis. Study of the underlying molecular mechanisms is essential so as to improve therapeutic strategies and to develop new pharmacological agents that may prevent or improve the course of this malignancy. Transforming growth factor-beta (TGF-β) intervenes in the process of hepatic fibrogenesis and cirrhosis, two pathogenic preconditions for the formation and progression of HCC [1] [2]. In addition, TGF-β plays a crucial role in the molecular pathogenesis of HCC and may, therefore, prove to be a promising drug target. We and other authors have recently demonstrated that inhibition of the TGF-β signaling pathway results in a synergistic downstream action with an inhibitory effect on the progression of HCC. Several TGF-β inhibitors have recently been developed, most of which are still in a preclinical phase, but they may soon be available for testing in patients with HCC. However, well-designed clinical trials will be needed to evaluate the effectiveness of these new agents prior to routine use in the clinic. Aim of this article is to make a brief review of the benefits and limitations of targeting the TGF-β signaling pathway in HCC.
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Cite this article as:
Mazzocca Antonio, Antonaci Salvatore and Giannelli Gianluigi, The TGF-β Signaling Pathway as a Pharmacological Target in a Hepatocellular Carcinoma, Current Pharmaceutical Design 2012; 18 (27) . https://dx.doi.org/10.2174/138161212802430431
DOI https://dx.doi.org/10.2174/138161212802430431 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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