Targeting the PI3K/mTOR pathway in idiopathic pulmonary fibrosis: Advances and therapeutic potential

• Published in: Bioorganic & medicinal chemistry 2024-12, Vol.115, p.117908, Article 117908
• Main Authors: Wang, Zhengyang, Guo, Yanzhi, Li, Kaiyin, Huo, Yan, Wang, Shuyan, Dong, Suzhen, Ma, Mingliang
• Format: Article
• Language: English
• Subjects: Collagen deposition; Idiopathic pulmonary fibrosis; PI3K/mTOR signalling pathway; Targeted therapy
• ISSN: 0968-0896; 1464-3391; 1464-3391
• DOI: 10.1016/j.bmc.2024.117908

[Display omitted] Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease characterized by irreversible tissue scarring, leading to severe respiratory dysfunction. Despite current treatments with the drugs Pirfenidone and Nintedanib, effective management of IPF remains inadequate due to limited therapeutic benefits and significant side effects. This review focuses on the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway, a critical regulator of cellular processes linked to fibrosis, such as fibroblast proliferation, inflammation, and epithelial-mesenchymal transition (EMT). We discuss recent advances in understanding the role of the PI3K/mTOR pathway in IPF pathogenesis and highlight emerging therapies targeting this pathway. The review compiles evidence from both preclinical and clinical studies, suggesting that PI3K/mTOR inhibitors may offer new hope for IPF treatment by modulating fibrosis and improving patient outcomes. Moreover, it outlines the potential for these inhibitors to be developed into effective, personalized treatment options, underscoring the importance of further research to explore their efficacy and safety profiles comprehensively.