title: The rationale for targeting TGF-β in chronic liver diseases.
abstract: BACKGROUND
  Transforming growth factor (TGF)-β is a pluripotent cytokine that displays several tissue-specific biological activities. In the liver, TGF-β is considered a fundamental molecule, controlling organ size and growth by limiting hepatocyte proliferation. It is involved in fibrogenesis and, therefore, in worsening liver damage, as well as in triggering the development of hepatocellular carcinoma (HCC). TGF-β is known to act as an oncosuppressor and also as a tumour promoter in HCC, but its role is still unclear.
  
  
  METHODS
  In this review, we discuss the potential role of TGF-β in regulating the tumoural progression of HCC, and therefore the rationale for targeting this molecule in patients with HCC.
  
  
  RESULTS
  A considerable amount of experimental preclinical evidence suggests that TGF-β is a promising druggable target in patients with HCC. To support this hypothesis, a phase II clinical trial is currently ongoing using a TGF-β pathway inhibitor, and results will soon be available.
  
  
  CONCLUSIONS
  The identification of new TGF-β related biomarkers will help to select those patients most likely to benefit from therapy aimed at inhibiting the TGF-β pathway. New formulations that may provide a more controlled and sustained delivery of the drug will improve the therapeutic success of such treatments.
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Gianluigi
authors.identifier: http://orcid.org/0000-0002-5140-8060
authors.initials: G
authors.lastname: Giannelli
authors.affiliation: Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mikulits
authors.affiliation: Department of Medicine II, Medical Faculty, Mannheim Heidelberg University, Heidelberg, Germany.
authors.forename: Steven
authors.initials: S
authors.lastname: Dooley
authors.affiliation: Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fabregat
authors.affiliation: Department of Medical Biochemistry and Microbiology and Ludwig Institute for Cancer Research, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: Aristidis
authors.initials: A
authors.lastname: Moustakas
authors.affiliation: Department of Molecular Cell Biology, Cancer Genomics Centre Netherlands, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: ten Dijke
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Portincasa
authors.affiliation: GenXPro GmbH, Frankfurt, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Winter
authors.affiliation: Galapagos, Leiden, the Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: Janssen
authors.affiliation: CNR NANOTEC - Institute of Nanotechnology, Lecce, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Leporatti
authors.affiliation: Dep. Bioquímica y Biología Molecular II, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense, Madrid, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Herrera
authors.affiliation: Dep. Bioquímica y Biología Molecular II, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense, Madrid, Spain.
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Sanchez
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000503:physiopathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000503:physiopathology; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D016212:Transforming Growth Factor beta
keywords: EMT; HCC; TGF-β; galunisertib; targeting TGF-βRI; tumour progression