title: Transforming growth factor-β as a therapeutic target in hepatocellular carcinoma.
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.
authors.affiliation: Authors' Affiliations: Department of Biomedical Science and Human Oncology, University of Bari Medical School, Bari; Department of Internal Medicine, University of Modena and Reggio, Modena, Italy; and Early Phase Clinical Investigation, Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Giannelli
authors.forename: Erica
authors.initials: E
authors.lastname: Villa
authors.forename: Michael
authors.initials: M
authors.lastname: Lahn
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D002986:Clinical Trials as Topic; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011720:Pyrazoles / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000502:physiology; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D011720:Pyrazoles; D011804:Quinolines; D016212:Transforming Growth Factor beta; D000509:alpha-Fetoproteins; C557799:LY-2157299