The AKT-mTOR Signaling Pathway for Drug Response Prediction and Prognostic Signatures

The PI3K-AKT-mTOR signaling cascade is a prominent deregulated pathway in tumorigenesis and cancer progression. Genomic studies have revealed that different members of this pathway are mutated across different tumors, but the mutation status itself often does not predict the protein activation status of the signaling network. In the context of targeted therapy, the functional exploration of the PI3K-AKT-mTOR signaling network represents a novel approach for the stratification of the patients toward more specific treatments. Because phosphorylation is the main post-translational modification involved in the functional activation of the signaling cascade, several studies have evaluated the role of PI3K activation in conjunction with its downstream substrates as prognostic and predictive biomarkers for response to therapy. Due to the emerging importance of functional proteomic studies in the identification of predictive and prognostic biomarkers, different technologies have been developed to investigate the human kinome and its activation. This chapter will provide an overview of the role of the PI3K-AKT-mTOR signaling network as a predictive and prognostic biomarker across different tumors along with a panel of high throughput and multiplex technologies used to broadly investigate functional changes.