Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Bioorg Med Chem. 2024 Dec 1;115:117908. doi: 10.1016/j.bmc.2024.117908. Epub 2024 Sep 5.
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.
特发性肺纤维化（IPF）是一种进行性、致命性肺部疾病，其特征为不可逆转的组织瘢痕形成，导致严重的呼吸功能障碍。尽管目前有吡非尼酮和尼达尼布等药物治疗，但由于治疗效果有限且存在严重副作用，IPF 的有效管理仍不足。本文重点介绍磷酸肌醇 3-激酶（PI3K）/雷帕霉素靶蛋白（mTOR）信号通路，该通路是与纤维化相关的细胞过程（如成纤维细胞增殖、炎症和上皮-间充质转化（EMT））的关键调节因子。我们讨论了目前对 PI3K/mTOR 通路在 IPF 发病机制中的作用的理解，并强调了针对该通路的新兴治疗方法。本文综述了来自临床前和临床研究的证据，表明 PI3K/mTOR 抑制剂通过调节纤维化和改善患者预后，为 IPF 治疗提供了新的希望。此外，本文还概述了这些抑制剂有可能开发成为有效的、个性化的治疗选择，强调了进一步研究以全面探索其疗效和安全性的重要性。
