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Activation of mTOR Signaling Pathway in Hepatocellular Carcinoma

Authors
  • Ferrín, Gustavo1, 2
  • Guerrero, Marta1, 3
  • Amado, Víctor1, 3
  • Rodríguez-Perálvarez, Manuel1, 2, 3
  • De la Mata, Manuel1, 2, 3
  • 1 (M.D.l.M.)
  • 2 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 14004 Córdoba, Spain
  • 3 Department of Hepatology and Liver Transplantaton, Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Feb 13, 2020
Volume
21
Issue
4
Identifiers
DOI: 10.3390/ijms21041266
PMID: 32070029
PMCID: PMC7072933
Source
PubMed Central
Keywords
License
Green

Abstract

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and occurs mainly in patients with liver cirrhosis. The mammalian target of rapamycin (mTOR) signaling pathway is involved in many hallmarks of cancer including cell growth, metabolism re-programming, proliferation and inhibition of apoptosis. The mTOR pathway is upregulated in HCC tissue samples as compared with the surrounding liver cirrhotic tissue. In addition, the activation of mTOR is more intense in the tumor edge, thus reinforcing its role in HCC proliferation and spreading. The inhibition of the mTOR pathway by currently available pharmacological compounds (i.e., sirolimus or everolimus) is able to hamper tumor progression both in vitro and in animal models. The use of mTOR inhibitors alone or in combination with other therapies is a very attractive approach, which has been extensively investigated in humans. However, results are contradictory and there is no solid evidence suggesting a true benefit in clinical practice. As a result, neither sirolimus nor everolimus are currently approved to treat HCC or to prevent tumor recurrence after curative surgery. In the present comprehensive review, we analyzed the most recent scientific evidence while providing some insights to understand the gap between experimental and clinical studies.

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