AKT in cancer: new molecular insights and advances in drug development

• Published in: British journal of clinical pharmacology Vol. 82; no. 4; pp. 943 - 956
• Main Authors: Mundi, Prabhjot S., Sachdev, Jasgit, McCourt, Carolyn, Kalinsky, Kevin
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.10.2016
• Subjects: Animals; Carcinogenesis - drug effects; clinical oncology; Humans; medical oncology; Molecular Targeted Therapy - methods; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - metabolism; Neoplasms - pathology; Phosphatidylinositol 3-Kinases - physiology; phosphatidylinositol 3‐kinases; protein kinase B; Proto-Oncogene Mas; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - physiology; proto‐oncogene proteins c‐AKT; proto‐oncogene proteins c‐AKT/genetics; proto‐oncogene proteins c‐AKT/metabolism; Review; Reviews; Signal Transduction - drug effects; signal transduction/physiology; medical oncology; phosphatidylinositol 3-kinases; proto-oncogene proteins c-AKT/genetics; signal transduction/physiology; proto-oncogene proteins c-AKT; proto-oncogene proteins c-AKT/physiology; proto-oncogene proteins c-AKT/metabolism; clinical oncology; protein kinase B
• ISSN: 0306-5251; 1365-2125; 1365-2125
• DOI: 10.1111/bcp.13021

The phosphatidylinositol‐3 kinase (PI3K)–AKT pathway is one of the most commonly dysregulated pathways in all of cancer, with somatic mutations, copy number alterations, aberrant epigenetic regulation and increased expression in a number of cancers. The carefully maintained homeostatic balance of cell division and growth on one hand, and programmed cell death on the other, is universally disturbed in tumorigenesis, and downstream effectors of the PI3K–AKT pathway play an important role in this disturbance. With a wide array of downstream effectors involved in cell survival and proliferation, the well‐characterized direct interactions of AKT make it a highly attractive yet elusive target for cancer therapy. Here, we review the salient features of this pathway, evidence of its role in promoting tumorigenesis and recent progress in the development of therapeutic agents that target AKT.