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

Meran Keshawa Ediriweera; Kamani Hemamala Tennekoon; Sameera Ranganath Samarakoon

doi:10.1016/j.semcancer.2019.05.012

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.

Authors

Meran Keshawa Ediriweera¹, Kamani Hemamala Tennekoon², Sameera Ranganath Samarakoon²

Affiliations

¹ Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka. Electronic address: mk.ediriweera@gmail.com.
² Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka.

PMID: 31128298
DOI: 10.1016/j.semcancer.2019.05.012

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
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases