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

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.

• Authors: George Mihai Nitulescu, Maryna Van De Venter, Georgiana Nitulescu, Anca Ungurianu, Petras Juzenas, Qian Peng, Octavian Tudorel Olaru, Daniela Grădinaru, Aristides Tsatsakis, Dimitris Tsoukalas, Demetrios A Spandidos, Denisa Margina
• Journal: International journal of oncology (Int J Oncol) Vol. 53 Issue 6 Pg. 2319-2331 (Dec 2018) ISSN: 1791-2423 [Electronic] Greece
• PMID: 30334567 (Publication Type: Journal Article, Review)

Chemical References

• Protein Kinase Inhibitors
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Clinical Trials as Topic
• Humans
• Neoplasms (drug therapy, metabolism)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-akt (chemistry, metabolism)
• Signal Transduction (drug effects)