Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

Mol Biol Rep. 2020 Jun;47(6):4587-4629. doi: 10.1007/s11033-020-05435-1. Epub 2020 Apr 24.

Abstract

Given that the PI3K/AKT pathway has manifested its compelling influence on multiple cellular process, we further review the roles of hyperactivation of PI3K/AKT pathway in various human cancers. We state the abnormalities of PI3K/AKT pathway in different cancers, which are closely related with tumorigenesis, proliferation, growth, apoptosis, invasion, metastasis, epithelial-mesenchymal transition, stem-like phenotype, immune microenvironment and drug resistance of cancer cells. In addition, we investigated the current clinical trials of inhibitors against PI3K/AKT pathway in cancers and found that the clinical efficacy of these inhibitors as monotherapy has so far been limited despite of the promising preclinical activity, which means combinations of targeted therapy may achieve better efficacies in cancers. In short, we hope to feature PI3K/AKT pathway in cancers to the clinic and bring the new promising to patients for targeted therapies.

Keywords: AKT; Cancer; PI3K; PTEN; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Cell Transformation, Neoplastic / genetics
  • Epithelial-Mesenchymal Transition / physiology
  • Humans
  • Neoplasms / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol 3-Kinases / physiology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-akt / physiology
  • Signal Transduction / physiology
  • Tumor Microenvironment / physiology

Substances

  • Proto-Oncogene Proteins c-akt