title: The PI3K/Akt/PTEN/mTOR pathway: a fruitful target for inducing cell death in rheumatoid arthritis?
abstract: PI3K/Akt/mTOR signaling regulates diverse cellular processes. Abnormal PI3K/Akt/mTOR signaling is a characteristic feature of cancer. As such inhibition of PI3K/Akt/mTOR signaling using small molecule inhibitors has been a focus of recently developed anticancer drugs. Rheumatoid arthritis and psoriatic arthritis are autoimmune-mediated inflammatory diseases. PI3K signaling could now be targeted to determine its contribution to rheumatoid and psoriatic arthritis where deregulated proliferation and aberrant survival of activated immune cells, macrophages, monocytes, dendritic cells and synovial fibroblasts significantly overlap with abnormal growth of cancer cells. The results of some recent studies in psoriatic arthritis using PI3K signaling inhibitors suggests that small molecule inhibitor strategies directed at PI3K signaling may be a useful future therapy for immune-mediated arthritis.
authors.affiliation: Department of Medicine, Division of Rheumatic Diseases, University Hospitals, Case Medical Center, Foley Medical Building, Room 207, 2061 Cornell Road, Cleveland, OH 44106, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Malemud
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D015535:Arthritis, Psoriatic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D054852:Small Molecule Libraries; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human