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.
