Targeting the phosphatidylinositol 3-kinase pathway in multiple myeloma.
Multiple myeloma is a plasma cell neoplasm with a median survival of 3 to 5 years. Recent advances have improved patient outlook, but the disease remains incurable. Therefore, continued efforts to develop new therapies that target aberrant signaling pathways are needed. The phosphatidylinositol 3-kinase pathway regulates apoptosis, cell cycle regulation, and tumor proliferation. This pathway is constitutively activated in multiple myeloma and its inhibition induces apoptosis. Advances in understanding the signaling cascades mediating proliferation and survival of multiple myeloma cells have markedly improved the treatment of this disease. In this article, we review the role of the phosphatidylinositol 3-kinase/Akt pathway in the pathogenesis of multiple myeloma and the potential therapeutic implications of targeting this pathway in the treatment of multiple myeloma.
Younes
Hashem
H
Department of Internal Medicine, Division of Hematology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Leleu
Xavier
X
Hatjiharissi
Evdoxia
E
Moreau
Anne-Sophie
AS
Hideshima
Teru
T
Richardson
Paul
P
Anderson
Kenneth C
KC
Ghobrial
Irene M
IM
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008954:Models, Biological; D009101:Multiple Myeloma / Q000201:enzymology* / Q000401:mortality* / Q000628:therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D018841:HSP90 Heat-Shock Proteins; D015850:Interleukin-6; D019869:Phosphatidylinositol 3-Kinases