title: AKT as a therapeutic target in multiple myeloma.
abstract: BACKGROUND
  Multiple myeloma remains an incurable malignancy with poor survival. Novel therapeutic approaches capable of improving outcomes in patients with multiple myeloma are urgently required. AKT is a central node in the phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin signaling pathway with high expression in advanced and resistant multiple myeloma. AKT contributes to multiple oncogenic functions in multiple myeloma which may be exploited therapeutically. Promising preclinical data has lent support for pursuing further development of AKT inhibitors in multiple myeloma. Lead drugs are now entering the clinic.
  
  
  METHODS
  The rationale for AKT inhibition in multiple myeloma, pharmacological subtypes of AKT inhibitors in development, available results of clinical studies of AKT inhibitors and suitable drug partners for further development in combination with AKT inhibition in multiple myeloma are discussed.
  
  
  CONCLUSIONS
  AKT inhibitors are a welcome addition to the armamentarium against multiple myeloma and promising clinical activity is being reported from ongoing trials in combination with established and/or novel treatment approaches. AKT inhibitors may be set to improve patient outcomes when used in combination with synergistic drug partners.
authors.affiliation: Galway University Hospital, Department of Haematology , Newcastle Road, Galway , Ireland.
authors.forename: Niamh A
authors.initials: NA
authors.lastname: Keane
authors.forename: Siobhan V
authors.initials: SV
authors.lastname: Glavey
authors.forename: Janusz
authors.initials: J
authors.lastname: Krawczyk
authors.forename: Michael
authors.initials: M
authors.lastname: O'Dwyer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D015195:Drug Design; D004357:Drug Synergism; D006801:Humans; D058990:Molecular Targeted Therapy; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; AKT inhibitor; ATP-competitive; MK-2206; afuresertib; alkylphospholipid; allosteric inhibitor; multiple myeloma; perifosine; phosphatidylinositol-3-kinase; pleckstrin homology domain; triciribine