Targeting the AKT pathway in ovarian cancer

Abstract

The PI3K/AKT pathway is an oncogenic pro-survival pathway mediating key cellular functions, such as cell cycle progression, growth, proliferation, metabolism and survival. In ovarian cancer, alterations have been observed in both the catalytic and regulatory subunits of the PI3K enzyme, in the opposing phosphatase PTEN and in each of the three isoforms of AKT itself. The net effect is a frequent hyperactivation of the pathway which has been linked to poor prognosis and chemoresistance. An ever-increasing depth of knowledge and understanding of how this pathway is regulated and dysregulated in normal tissues and in cancer has highlighted the attractiveness of developing a range of therapeutic strategies aimed at specifically targeting this pathway in order to restore growth control and apoptotic response to tumour cells. We describe here the biological basis of the AKT pathway and its role in ovarian cancer and summarise the current progress in developing clinically applicable inhibitors of AKT pathway components for potential use in the ovarian cancer setting either alone or in combination with conventional cytotoxic agents such as the platinum drugs. © 2011 Springer Science+Business Media, LLC.