Targeting the PI3K/Akt/mTOR Pathway in Hepatocellular Carcinoma
Eun Jin Sun,
Miriam Wankell,
Pranavan Palamuthusingam,
Craig McFarlane,
Lionel Hebbard
Affiliations
Eun Jin Sun
Centre for Molecular Therapeutics, Department of Molecular and Cell Biology, Australian Institute of Tropical Medicine and Health, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD 4811, Australia
Miriam Wankell
Centre for Molecular Therapeutics, Department of Molecular and Cell Biology, Australian Institute of Tropical Medicine and Health, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD 4811, Australia
Pranavan Palamuthusingam
Institute of Surgery, The Townsville University Hospital, Townsville, QLD 4811, Australia
Craig McFarlane
Centre for Molecular Therapeutics, Department of Molecular and Cell Biology, Australian Institute of Tropical Medicine and Health, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD 4811, Australia
Lionel Hebbard
Centre for Molecular Therapeutics, Department of Molecular and Cell Biology, Australian Institute of Tropical Medicine and Health, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD 4811, Australia
Despite advances in the treatment of cancers through surgical procedures and new pharmaceuticals, the treatment of hepatocellular carcinoma (HCC) remains challenging as reflected by low survival rates. The PI3K/Akt/mTOR pathway is an important signaling mechanism that regulates the cell cycle, proliferation, apoptosis, and metabolism. Importantly, deregulation of the PI3K/Akt/mTOR pathway leading to activation is common in HCC and is hence the subject of intense investigation and the focus of current therapeutics. In this review article, we consider the role of this pathway in the pathogenesis of HCC, focusing on its downstream effectors such as glycogen synthase kinase-3 (GSK-3), cAMP-response element-binding protein (CREB), forkhead box O protein (FOXO), murine double minute 2 (MDM2), p53, and nuclear factor-κB (NF-κB), and the cellular processes of lipogenesis and autophagy. In addition, we provide an update on the current ongoing clinical development of agents targeting this pathway for HCC treatments.
