From Fibrosis to Malignancy: Mechanistic Intersections Driving Lung Cancer Progression

Background/Objectives: Pulmonary fibrosis (PF) and lung cancer (LC) are major global health challenges that share several pathogenic mechanisms despite their distinct clinical features. PF leads to progressive fibrotic remodeling and respiratory decline, while LC is characterized by uncontrolled proliferation, invasion, and metastasis. Growing evidence shows that PF markedly increases the risk of LC development. This review aims to clarify the convergent molecular and cellular mechanisms that link fibrogenesis to tumorigenesis. Methods: Published studies exploring shared pathogenic pathways, molecular signaling networks, immune microenvironment alterations, and mitochondrial and genomic disturbances in PF and LC were systematically examined and integrated to identify common mechanisms contributing to fibrosis-associated carcinogenesis. Results: Findings highlight several overlapping processes between PF and LC, including oxidative stress, genomic instability, dysregulated DNA damage repair, immune microenvironment remodeling, mitochondrial dysfunction, and alterations in the ubiquitin-proteasome system. These aberrations drive chronic inflammation, epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and other hallmarks shared by both diseases. Key signaling pathways-such as transforming growth factor-β (TGF-β), programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1), and tumor microenvironment-mediated immune evasion-further contribute to disease progression and increased LC risk in PF patients. Conclusions: Integrating molecular and pathological insights reveals a strong biological continuum between PF and LC. Understanding these convergent mechanisms may facilitate the identification of diagnostic biomarkers and therapeutic targets, ultimately helping to mitigate PF-associated lung carcinogenesis.