title: AKT in cancer: new molecular insights and advances in drug development.
abstract: 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.
authors.affiliation: Division of Medical Oncology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.|Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
authors.forename: Prabhjot S
authors.initials: PS
authors.lastname: Mundi
authors.affiliation: Translational Genomics Research Institute, Virginia G. Piper Cancer Center at HonorHealth, Scottsdale, AZ, USA.
authors.forename: Jasgit
authors.initials: J
authors.lastname: Sachdev
authors.affiliation: Division of Gynecologic Oncology, Washington University School of Medicine in St Louis, St Louis, MO, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: McCourt
authors.affiliation: Division of Medical Oncology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA. kk2693@cumc.columbia.edu.|Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA. kk2693@cumc.columbia.edu.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kalinsky
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt; C000715470:MAS1 protein, human
keywords: clinical oncology; medical oncology; phosphatidylinositol 3-kinases; protein kinase B; proto-oncogene proteins c-AKT; proto-oncogene proteins c-AKT/genetics; proto-oncogene proteins c-AKT/metabolism; proto-oncogene proteins c-AKT/physiology; signal transduction/physiology