PI3K/AKT/mTOR Signalling Pathways as Therapeutic Targets: From Biomarkers to Clinical Outcomes.

Abstract

The PI3K/AKT/mTOR signalling pathway is crucial in cellular growth, proliferation, metabolism and survival and is frequently dysregulated in a wide range of malignancies, contributing to tumor progression, therapy resistance, and poor patient outcome. However, the molecular targeting of the signalling pathway in cancer remains uncertain. In this review, we summarise the current evidence surrounding the PI3K/AKT/mTOR signalling pathway as a therapeutic target with consideration given to its role as a biomarker. Methods: A systematic review was carried out via PRISMA guidelines. Databases of publications including PubMed, Scopus, Web of Science, and the Cochrane Library were searched for studies published from January 2014 to December of the search period. Relevant studies that investigated the molecular alterations of the PI3K/AKT/mTOR signalling pathway and targeted the therapeutic agents and their clinical uses targeting this pathway were included. Reports were screened for rejection before proceeding to the full text stage till a total of 1,463 records were restored, of which 43 studies fulfilled the inclusion criteria. The report suggests that aberrations in the PI3K/AKT/mTOR signalling pathway, whether by mutation, amplification, or loss of control over its normal regulatory actions correlates with tumour aggressiveness and resistance to common therapies, however targeted agents such as PI3K inhibitors, AKT inhibitors, and mTOR inhibitors remains a mixed and uncertain bag. The use of molecular biomarkers enhance the prediction on selected populations on patient prognosis, however maturity of this field is still required.