Molecular mechanisms and emerging therapeutics in pulmonary fibrosis: A recent update

Pulmonary fibrosis (PF) is a chronic, progressive, and fatal lung disorder characterized by injury to alveolar epithelial cells (AECs), the formation of activated fibroblast/myofibroblast foci, and an excessive buildup of extracellular matrix (ECM). Current treatment strategies include the administration of two main drugs, viz., pirfenidone and nintedanib. However, there is no cure for PF; thus, there is a dire need to understand the pathophysiology of PF better and identify potential novel targets for PF. This review aims to provide a recent update on the signaling pathways contributing to the intricacies of cell signaling mechanisms driving fibrogenesis, including TGF-β, Hippo-YAP, NF-κB, inflammation, and Wnt/β-catenin. Additionally, the discussion covers emerging therapeutic strategies directed against such signaling networks, focusing on some of the most promising molecular strategies to halt or reverse fibrotic processes. Additionally, we discuss preclinical studies revealing the in vitro efficacy and safety, and the current clinical status of new therapeutic agents in PF. The synergy of preclinical and clinical studies' findings will allow this review to critically evaluate current therapeutic directions and emerging trends in PF management, shaping a future course of research and clinical application.