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Transforming Growth Factor-β as a Therapeutic Target in Hepatocellular Carcinoma
- Source :
- Cancer Research. 74:1890-1894
- Publication Year :
- 2014
- Publisher :
- American Association for Cancer Research (AACR), 2014.
-
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.
- Subjects :
- Cancer Research
Carcinoma, Hepatocellular
Epithelial-Mesenchymal Transition
Paracrine signalling
Transforming Growth Factor beta
Carcinoma
medicine
Humans
Galunisertib
Epithelial–mesenchymal transition
Autocrine signalling
Clinical Trials as Topic
Liver Neoplasms
Pyrazoles
Quinolines
Signal Transduction
alpha-Fetoproteins
biology
business.industry
Transforming growth factor beta
medicine.disease
Oncology
Tumor progression
Hepatocellular carcinoma
Immunology
Cancer research
biology.protein
business
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 74
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....88e37562009a025946870d45be65d635