Tomos Ioannis, Kanellopoulou Paraskevi, Nastos Dimitris, Aidinis Vassilis
5th Department of Respiratory Medicine, 'SOTIRIA' Chest Diseases Hospital of Athens, Athens, Greece.
Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center Alexander Fleming, Athens, Greece.
Expert Opin Ther Targets. 2025 Jan-Feb;29(1-2):43-57. doi: 10.1080/14728222.2025.2471579. Epub 2025 Feb 27.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with a dismal prognosis. While the standard-of-care (SOC) drugs approved for IPF represent a significant advancement in antifibrotic therapies, they primarily slow disease progression and have limited overall efficacy and many side effects. Consequently, IPF remains a condition with high unmet medical and pharmacological needs.
A wide variety of molecules and mechanisms have been implicated in the pathogenesis of IPF, many of which have been targeted in clinical trials. In this review, we discuss the latest therapeutic targets that affect extracellular matrix (ECM) homeostasis and the activation of lung fibroblasts, with a specific focus on ECM invasion.
A promising new approach involves targeting ECM invasion by fibroblasts, a process that parallels cancer cell behavior. Several cancer drugs are now being tested in IPF for their ability to inhibit ECM invasion, offering significant potential for future treatments. The delivery of these therapies by inhalation is a promising development, as it may enhance local effectiveness and minimize systemic side effects, thereby improving patient safety and treatment efficacy.
特发性肺纤维化（IPF）是一种慢性、进行性间质性肺疾病，预后不佳。虽然批准用于IPF的标准治疗（SOC）药物代表了抗纤维化治疗的重大进展，但它们主要是减缓疾病进展，总体疗效有限且有许多副作用。因此，IPF仍然是一种存在高度未满足医疗和药理学需求的疾病。
多种分子和机制与IPF的发病机制有关，其中许多已在临床试验中作为靶点。在本综述中，我们讨论影响细胞外基质（ECM）稳态和肺成纤维细胞激活的最新治疗靶点，特别关注ECM侵袭。
一种有前景的新方法是靶向成纤维细胞的ECM侵袭，这一过程与癌细胞行为相似。目前几种癌症药物正在IPF中测试其抑制ECM侵袭的能力，为未来治疗提供了巨大潜力。通过吸入给药这些疗法是一个有前景的发展方向，因为它可能提高局部疗效并将全身副作用降至最低，从而提高患者安全性和治疗效果。
