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The rationale for targeting TGF-beta in chronic liver diseases
Univ Bari, Dept Biomed Sci & Human Oncol, Sch Med, Bari, Italy..
Med Univ Vienna, Ctr Comprehens Canc, Div Inst Canc Res, Dept Med 1, Vienna, Austria..
Mannheim Heidelberg Univ, Fac Med, Dept Med 2, Heidelberg, Germany..
Bellvitge Biomed Res Inst IDIBELL, Barcelona, Spain..
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2016 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 46, no 4, 349-361 p.Article, review/survey (Refereed) PublishedText
Abstract [en]

BackgroundTransforming growth factor (TGF)- is a pluripotent cytokine that displays several tissue-specific biological activities. In the liver, TGF- 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- is known to act as an oncosuppressor and also as a tumour promoter in HCC, but its role is still unclear. DesignIn this review, we discuss the potential role of TGF- in regulating the tumoural progression of HCC, and therefore the rationale for targeting this molecule in patients with HCC. ResultsA considerable amount of experimental preclinical evidence suggests that TGF- is a promising druggable target in patients with HCC. To support this hypothesis, a phase II clinical trial is currently ongoing using a TGF- pathway inhibitor, and results will soon be available. ConclusionsThe identification of new TGF- related biomarkers will help to select those patients most likely to benefit from therapy aimed at inhibiting the TGF- pathway. New formulations that may provide a more controlled and sustained delivery of the drug will improve the therapeutic success of such treatments.

Place, publisher, year, edition, pages
2016. Vol. 46, no 4, 349-361 p.
Keyword [en]
EMT, galunisertib, HCC, targeting TGF-beta RI, TGF-beta, tumour progression
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-299081DOI: 10.1111/eci.12596ISI: 000373160900007PubMedID: 26823073OAI: oai:DiVA.org:uu-299081DiVA: diva2:948928
Funder
EU, European Research Council
Available from: 2016-07-14 Created: 2016-07-14 Last updated: 2016-07-14Bibliographically approved

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Moustakas, Aristidis
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Department of Medical Biochemistry and MicrobiologyLudwig Institute for Cancer Research
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