Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown origin that usually results in death from secondary respiratory failure within 2–5 years of diagnosis. Recent studies have identified key roles of cytokine and growth factor pathways in the pathogenesis of IPF. Although there have been numerous clinical trials of drugs investigating their efficacy in the treatment of IPF, only Pirfenidone and Nintedanib have been approved by the FDA. However, they have some major limitations, such as insufficient efficacy, undesired side effects and poor pharmacokinetic properties. To give more insights into the discovery of potential targets for the treatment of IPF, this review provides an overview of cytokines, growth factors and their signaling pathways in IPF, which have important implications for fully exploiting the therapeutic potential of targeting cytokine and growth factor pathways. Advances in the field of cytokine and growth factor pathways will help slow disease progression, prolong life, and improve the quality of life for IPF patients in the future.

Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

“…Chemokines and interleukins are also involved in recruitment of pro-fibrotic cells and formation of profibrotic microenvironment, as we discussed in our previous paper (Ma et al, 2022). However, CCL2, a key chemokine for monocyte/macrophage migration and infiltration, failed to demonstrate clinical benefit in a phase II clinical trial (NCT00786201).…”

“…JAK/STAT signaling ( Montero et al, 2021 ), receptor-type tyrosine kinase/non-receptor-type tyrosine kinase signaling (e.g., Src) ( Hu et al, 2014 ), PI3K/Akt/mTOR signaling ( Hennessy et al, 2005 ; Mercer et al, 2016 ; Lawrence and Nho, 2018 ), and Hedgehog signaling ( Effendi and Nagano, 2021 ) comprise complex fibrosis regulatory signaling pathway. In our previous reviews, we have discussed the aforementioned signaling pathways ( Ma et al, 2022 ).…”

Identification of diagnostic gene biomarkers related to immune infiltration in patients with idiopathic pulmonary fibrosis based on bioinformatics strategies

“…IPF has the characteristics of rapid progression, high fatality rate and poor prognosis, and the median survival after diagnosis in most patients is 2.5 to 3.5 years, with a five-year survival rate of only 20–40% ( 6 ). The pathogenesis of IPF has not yet been elucidated, and anti-inflammatory therapy is generally used clinically with glucocorticoids, immunosuppressants, cytotoxic agents or inhibitor (Pirfenidone and Nintedanib) ( 7 – 9 ). With the deepening of clinical research, researchers found that only 20% of IPF patients are sensitive to glucocorticoid therapy, and often transgender reactions(allergies: it is a type of immune reaction, a reaction that occurs after non-peptide drugs are combined with the body’s protein as a hapten to an antigen), there is no specific treatment plan for IPF in the clinic, coupled with the lack of specific clinical manifestations in the early stage of IPF, so the difficulty of diagnosis and treatment is high ( 10 , 11 ).…”

Avances en la investigación de los mecanismos moleculares, los blancos terapéuticos y el desarrollo de fármacos para la fibrosis pulmonar idiopática

“…Quimiocinas e interleucinas también están involucradas en el reclutamiento de células profibróticas y en la formación de un microambiente profibrótico, como discutimos en un artículo anterior [207]. Sin embargo, CCL2, una quimiocina clave para la migración e infiltración de monocitos/macrófagos, no mostró beneficio clínico en un ensayo de fase II (NCT00786201).…”

“…La señalización JAK/STAT [214], la señalización de tirosina quinasa de tipo receptor/no receptor (por ejemplo, Src) [215], la señalización PI3K/Akt/mTOR [216–218) y la señalización Hedgehog (Effendi y Nagano, 2021) constituyen una compleja vía de señalización reguladora de la fibrosis. En revisiones anteriores hemos discutido estas vías de señalización [207].…”