Premium
PI3K signalling in chronic obstructive pulmonary disease and opportunities for therapy
Author(s) -
Moradi Sharif,
Jarrahi Esmaeil,
Ahmadi Ali,
Salimian Jafar,
Karimi Mehrdad,
Zarei Azadeh,
Azimzadeh Jamalkandi Sadegh,
Ghanei Mostafa
Publication year - 2021
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5696
Subject(s) - copd , medicine , pi3k/akt/mtor pathway , disease , pulmonary disease , roflumilast , pathogenesis , clinical trial , signalling , inflammation , immunology , bioinformatics , signal transduction , biology , biochemistry , microbiology and biotechnology
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterised by airway inflammation and progressive obstruction of the lung airflow. Current pharmacological treatments include bronchodilators, alone or in combination with steroids, or other anti‐inflammatory agents, which have only partially contributed to the inhibition of disease progression and mortality. Therefore, further research unravelling the underlying mechanisms is necessary to develop new anti‐COPD drugs with both lower toxicity and higher efficacy. Extrinsic signalling pathways play crucial roles in COPD development and exacerbations. In particular, phosphoinositide 3‐kinase (PI3K) signalling has recently been shown to be a major driver of the COPD phenotype. Therefore, several small‐molecule inhibitors have been identified to block the hyperactivation of this signalling pathway in COPD patients, many of them showing promising outcomes in both preclinical animal models of COPD and human clinical trials. In this review, we discuss the critically important roles played by hyperactivated PI3K signalling in the pathogenesis of COPD. We also critically review current therapeutics based on PI3K inhibition, and provide suggestions focusing on PI3K signalling for the further improvement of the COPD phenotype. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.