Phosphatidylinositol 3-kinase isoforms as targets in respiratory disease.
Respiratory diseases such as chronic obstructive pulmonary disease [COPD], severe asthma, cystic fibrosis [CF] and idiopathic pulmonary fibrosis [IPF] are inadequately controlled by current therapies. The underlying molecular mechanisms and pathogenesis of these diseases remain unclear, making identification and validation of potential new therapeutic targets difficult. However, recent studies have identified the central signalling mediator PI3K as playing an integral role in the immune system including initiation and maintenance of inflammatory responses. Specifically, the relatively leukocyte-specific PI3Kgamma and PI3Kdelta isoforms are central to leukocyte function and can be targeted pharmacologically. Early to man studies using selective PI3K isoform inhibitors are required to determine whether they have a future in treating respiratory disease, particularly in controlling both innate and adaptive inflammatory responses as well as restoring glucocorticoid function and reducing tumorigenesis.
Marwick
John A
JA
Section of Airways Disease, National Heart and Lung Institute, Imperial College London, London, UK. j.marwick@imperial.ac.uk
Chung
Kian Fan
KF
Adcock
Ian M
IM
D000818:Animals; D016503:Drug Delivery Systems; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D007962:Leukocytes / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012140:Respiratory Tract Diseases / Q000188:drug therapy* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D005938:Glucocorticoids; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors