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Int J Oncol. 2018 Dec;53(6):2319-2331. doi: 10.3892/ijo.2018.4597. Epub 2018 Oct 16.

The Akt pathway in oncology therapy and beyond (Review).

Author information

1
Faculty of Pharmacy, 'Carol Davila' University of Medicine and Pharmacy, 020956 Bucharest, Romania.
2
Department of Biochemistry and Microbiology, Nelson Mandela University, Port Elizabeth 6031, South Africa.
3
Department of Pathology, Radiumhospitalet, Oslo University Hospital, 0379 Oslo, Norway.
4
Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece.
5
Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece.

Abstract

Protein kinase B (Akt), similar to many other protein kinases, is at the crossroads of cell death and survival, playing a pivotal role in multiple interconnected cell signaling mechanisms implicated in cell metabolism, growth and division, apoptosis suppression and angiogenesis. Akt protein kinase displays important metabolic effects, among which are glucose uptake in muscle and fat cells or the suppression of neuronal cell death. Disruptions in the Akt‑regulated pathways are associated with cancer, diabetes, cardiovascular and neurological diseases. The regulation of the Akt signaling pathway renders Akt a valuable therapeutic target. The discovery process of Akt inhibitors using various strategies has led to the identification of inhibitors with great selectivity, low side‑effects and toxicity. The usefulness of Akt emerges beyond cancer therapy and extends to other major diseases, such as diabetes, heart diseases, or neurodegeneration. This review presents key features of Akt structure and functions, and presents the progress of Akt inhibitors in regards to drug development, and their preclinical and clinical activity in regards to therapeutic efficacy and safety for patients.

PMID:
30334567
PMCID:
PMC6203150
DOI:
10.3892/ijo.2018.4597
[Indexed for MEDLINE]
Free PMC Article

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