Transforming growth factor-β as a therapeutic target in hepatocellular carcinoma

G Giannelli, E Villa, M Lahn - Cancer research, 2014 - AACR
Cancer research, 2014AACR
Hepatocellular carcinoma arises in patients as a consequence of long-standing preexisting
liver illnesses, including viral hepatitis, alcohol abuse, or metabolic disease. In such
preexisting liver diseases, TGF-β plays an important role in orchestrating a favorable
microenvironment for tumor cell growth and promoting epithelial–mesenchymal transition
(EMT). TGF-β signaling promotes hepatocellular carcinoma progression by two
mechanisms: first, via an intrinsic activity as an autocrine or paracrine growth factor and …
Abstract
Hepatocellular carcinoma arises in patients as a consequence of long-standing preexisting liver illnesses, including viral hepatitis, alcohol abuse, or metabolic disease. In such preexisting liver diseases, TGF-β plays an important role in orchestrating a favorable microenvironment for tumor cell growth and promoting epithelial–mesenchymal transition (EMT). TGF-β signaling promotes hepatocellular carcinoma progression by two mechanisms: first, via an intrinsic activity as an autocrine or paracrine growth factor and, second, via an extrinsic activity by inducing microenvironment changes, including cancer-associated fibroblasts, T regulatory cells, and inflammatory mediators. Although there is an increasing understanding on how TGF-β signaling is associated with tumor progression in hepatocellular carcinoma, it is not clear whether TGF-β signaling is limited to a certain subgroup of patients with hepatocellular carcinoma or is a key driver of hepatocellular carcinoma during the entire tumorigenesis of hepatocellular carcinoma. Inhibitors of the TGF-β signaling have been shown to block hepatocellular carcinoma growth and progression by modulating EMT in different experimental models, leading to the clinical investigation of the TGF-β inhibitor LY2157299 monohydrate in hepatocellular carcinoma. Preliminary results from a phase II clinical trial have shown improved clinical outcome and also changes consistent with a reduction of EMT. Cancer Res; 74(7); 1890–4. ©2014 AACR.
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