Treatment of pulmonary fibrosis: From disease mechanisms to future novel therapies (Review)

Pulmonary fibrosis (PF) is a progressive and fatal interstitial lung disease characterized by irreversible lung scarring and frequently associated with lung cancer. Currently, there remains a lack of effective therapies capable of significantly improving long‑term outcomes or reversing the disease course. Although antifibrotic drugs are widely used and have enhanced the mechanistic understanding of PF, their efficacy is limited. This review systematically explores the core pathobiological processes and epigenetic regulatory networks involved in PF pathogenesis. Simultaneously, a critical review of the most promising emerging therapeutic strategies in recent years, including stem cell therapy, novel targeted agents, nucleic acid delivery technologies and epigenetic interventions, is provided. An in‑depth analysis of the transformative role of artificial intelligence (AI) in integrating multi‑omics data, predicting disease trajectories and optimizing personalized treatment plans is also presented. However, significant challenges hinder the clinical translation of these novel approaches. While AI‑based models offer valuable insights, they are constrained by the complex heterogeneity of PF. Epigenetic therapies, despite their promise, face obstacles related to drug development, delivery efficiency and long‑term clinical impact. Moving forward, the fundamental shift from palliative management to a disease‑modifying paradigm for PF will not rely on a single technological breakthrough. Instead, it necessitates deep interdisciplinary integration. This involves the systematic convergence of the potential of regenerative medicine, the precision of gene editing, the molecular intervention of targeted therapy and the dynamic decision‑making capabilities driven by AI. The goal is to construct a next‑generation, individualized treatment framework capable of adapting to disease heterogeneity and evolving with the patient's condition. Despite the considerable challenges, this multimodal integrated strategy is paving a viable new path toward ultimately conquering pulmonary fibrosis.