Regulation of the PI3K-Akt Network: Current Status and a Promise for the Treatment of Human Diseases

Masayuki      Noguchi; Toshiyuki      Obata; Futoshi      Suizu

Abstract

The growth factor signals regulate the balance of cell proliferation and cell death to maintain the homeostasis in vivo; hence, deregulation of the balance underlies a variety of human diseases. The PI3K-Akt network is activated by various cytokines or growth factors and mediates intracellular signals to regulate a wide variety of cellular responses, including anti-apoptosis, proliferation, cell cycling, protein synthesis, glucose metabolism, and telomere activity. Genomic mutations, alterations, amplifications, and/or translocations of the oncogenes, tumor suppressor genes, or kinases involved in the PI3K-Akt regulatory network underlie various human diseases such as cancers, viral infections, glucose intolerance (or diabetes mellitus), schizophrenia, and/or autoimmune diseases. Therefore, targeting the PI3K-Akt network becomes an attractive goal for drug development.This review article summarizes the current knowledge about the regulation of the PI3K-Akt signaling network to highlight therapeutic implications for human diseases.

Keywords: Phosphoinositide 3 Kinase, PI3K-Akt network, Akt, inhibitors, pharmacological compounds, cancer therapy