Dual roles of amino acid metabolic reprogramming in chronic airway diseases and lung cancer: therapeutic opportunities and challenges.

Amino acid metabolic reprogramming has emerged as a pivotal mechanism underlying the pathogenesis of chronic airway diseases and lung cancer. This review comprehensively examines the dynamic regulation and clinical implications of key amino acid pathways-including arginine, glutamine, and tryptophan metabolism-in chronic obstructive pulmonary disease (COPD), asthma, and lung malignancies. Our findings reveal a key difference in metabolic dysregulation between chronic airway diseases and lung cancer: while it drives persistent inflammation, oxidative stress, and tissue damage in chronic conditions, cancer cells exploit these same pathways to support their uncontrolled growth and create an immunosuppressive tumor microenvironment. Crucially, shared metabolic nodes reveal actionable targets for dual-purpose therapeutic strategies. Recent advances demonstrate the translational potential of metabolic interventions. Arginase inhibitors simultaneously improve vascular function in COPD and enhance antitumor immunity, while nanoparticle-delivered glutaminase blockers attenuate pulmonary fibrosis while curbing cancer progression. However, challenges persist in achieving tissue-specific delivery, real-time metabolic monitoring, and overcoming resistance. Future directions should focus on spatiotemporally controlled metabolic modulation and the development of multi-omics-based predictive models to usher in an era of precision metabolic therapy for respiratory disorders.