The role and mechanisms of the HIF-1 signaling pathway in LC-COPD

Chronic obstructive pulmonary disease (COPD) and lung cancer are highly correlated and frequently co-occur. Any degree of COPD significantly increases the risk of developing lung cancer, suggesting they may share common pathogenic mechanisms. The hypoxia-inducible factor 1 (HIF-1) signaling pathway, a complex regulatory network for cellular sensing and response to hypoxia, is abnormally activated in both COPD and lung cancer. Chronic inflammation, immune microenvironment imbalance, extracellular matrix remodeling, epithelial-mesenchymal transition, angiogenesis, and epithelial differentiation, all closely related to the HIF-1 pathway, lie at the intersection of both diseases. Consequently, the HIF-1 pathway is proposed as a potential molecular mechanism underpinning the occurrence, progression, and poor prognosis of lung cancer with COPD (LC-COPD). In this review, we focus on the role and mechanisms of HIF-1 in advancing LC-COPD, highlighting its promising potential as a therapeutic target.