Ferrín, GustavoGuerrero, MartaAmado, VíctorRodríguez-Perálvarez, ManuelDe la Mata, Manuel2022-06-282022-06-282020-02-13Ferrín G, Guerrero M, Amado V, Rodríguez-Perálvarez M, De la Mata M. Activation of mTOR Signaling Pathway in Hepatocellular Carcinoma. Int J Mol Sci. 2020 Feb 13;21(4):1266http://hdl.handle.net/10668/3716Hepatocellular 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/mTOREverolimusSirolimusHepatocellular carcinomaLiver transplantationSorafenibSerina-treonina quinasas TORCarcinoma hepatocelularTrasplante de hígadoMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms::Carcinoma, HepatocellularMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell ProliferationMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, NeoplasticMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver NeoplasmsMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm Recurrence, LocalMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal TransductionMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Lactones::Macrolides::SirolimusMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::TOR Serine-Threonine Kinasesreview article32070029open access10.3390/ijms210412661422-0067PMC7072933