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.