mTOR as a Potential Target for the Prevention and Treatment of Hepatocellular Carcinoma
Laura Elisa Buitrago-Molina,
Hepatocellular carcinoma (HCC) is a global health problem and responsible for up to 500.000 deaths annually.
It usually occurs secondary to infections with hepatitis B or C viruses, alcohol consumption, non-alcoholic steatohepatitis
or hereditary liver diseases. The prognosis for patients with advanced disease is dismal; therefore, new strategies to
prevent or treat this malignancy are urgently needed. Over recent years, several molecular pathways have been identified
contributing to the molecular pathogenesis of this devastating disease, among them the PI3K/AKT/mTOR pathway.
mTOR is effectively inhibited by rapamycin and its derivatives such as temsirolimus and everolimus. The anti-tumor
activity of rapamycin was identified more than 30 years ago in a screen performed at the National Cancer Institute, but
was subsequently not developed for cancer treatment. In the 1990s, activation of the mTOR pathway was recognized in
various malignancies spurring again the interest in mTOR inhibitors for anti-cancer treatment. In 2007, the US Food and
Drug Administration approved the first mTOR inhibitor, temsirolimus, for the treatment of renal cell carcinoma.
Currently, several clinical studies are underway to define the role of mTOR inhibitors for the treatment of hepatocellular
carcinoma. The aim of this review is to outline the role of mTOR for hepatocarcinogenesis. We will also discuss the latest
preclinical and clinical data of mTOR inhibitors for the prevention and treatment of HCC.
Keywords: Hepatocellular Carcinoma, mTOR, rapamycin, RAD001, Eukaryotic Translation Initiation Factor 4E- Binding Protein 1, Fumarylacetoacetate, Fumarylacetoacetate Hydrolase, Hepatitis B Virus, Hepatitis C Virus, Hypoxia-Inducible Factor-1, Hereditary Tyrosinemia type 1, Mammalian Target of Rapamycin, mTOR Complex 1, Phosphoinositide-3 Kinase, Vascular Endothelial Growth Factor
Rights & PermissionsPrintExport