Targeting the PI3K/AKT Pathway for the Treatment of Prostate Cancer

• Published in: Clinical cancer research 2009-08, Vol.15 (15), p.4799-4805
• Main Authors: Sarker, Debashis, Reid, Alison H M, Yap, Timothy A, de Bono, Johann S
• Format: Article
• Language: English
• Subjects: Androgen Receptor Antagonists; Chemokines - metabolism; Humans; Male; Oncogene Proteins, Fusion - metabolism; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; Receptors, Androgen - metabolism; Serine Endopeptidases - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Trans-Activators - metabolism; Transcriptional Regulator ERG
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-08-0125

Despite recent advances in our understanding of the biological basis of prostate cancer, the management of the disease, especially in the castration-resistant phase, remains a significant challenge. Deregulation of the phosphatidylinositol 3-kinase pathway is increasingly implicated in prostate carcinogenesis. In this review, we detail the role of this pathway in the pathogenesis of prostate cancer and the rapidly evolving therapeutic implications of targeting it. In particular, we highlight the importance of the appropriate selection of agents and combinations, and the critical role of predictive and pharmocodynamic biomarkers.