Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance

Semin Cancer Biol. 2019 Dec;59:147-160. doi: 10.1016/j.semcancer.2019.05.012. Epub 2019 May 22.

Abstract

Ovarian cancer (OC) is a lethal gynecological cancer. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the regulation of cell survival, growth, and proliferation. Irregularities in the major components of the PI3K/AKT/mTOR signaling pathway are common in human cancers. Despite the availability of strong pre-clinical and clinical data of PI3K/AKT/mTOR pathway inhibitors in OC, there is no FDA approved inhibitor available for the treatment of OC. Here, we outline the importance of PI3K/AKT/mTOR signaling pathway in OC tumorigenesis, proliferation and progression, and pre-clinical and clinical experience with several PI3K/AKT/mTOR pathway inhibitors in OC.

Keywords: AKT; Ovarian cancer; PI3K; Pathway; mTOR.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / etiology
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors / pharmacology
  • Phosphoinositide-3 Kinase Inhibitors / therapeutic use
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction* / drug effects
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt