The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism

Int J Mol Sci. 2023 Jan 31;24(3):2652. doi: 10.3390/ijms24032652.

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Metabolic reprogramming is considered a new hallmark of cancer, but it remains unclearly described in HCC. The dysregulation of the PI3K/AKT/mTOR signaling pathway is common in HCC and is, therefore, a topic of further research and the concern of developing a novel target for liver cancer therapy. In this review, we illustrate mechanisms by which this signaling network is accountable for regulating HCC cellular metabolism, including glucose metabolism, lipid metabolism, amino acid metabolism, pyrimidine metabolism, and oxidative metabolism, and summarize the ongoing clinical trials based on the inhibition of the PI3K/AKT/mTOR pathway in HCC.

Keywords: HCC treatment; amino acid metabolism; cancer therapy; glucose metabolism; lipid metabolism; oxidative metabolism; pyrimidine metabolism; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Carcinoma, Hepatocellular* / metabolism
  • Cell Line, Tumor
  • Humans
  • Liver Neoplasms* / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • MTOR protein, human