COPD–Lung Cancer Comorbidity: Mechanistic Insights and Precision Oncology Implications

Yajuan He, Beili Liu, Wenjun Li, Xinyi Zhou, Hongyan Tao Department of Pulmonary and Critical Care Medicine, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730000, People’s Republic of ChinaCorrespondence: Hongyan Tao, Department of Pulmonary and Critical Care Medicine, The Second Hospital & Clinical Medical School, Lanzhou University, 82 Cuiyingmen Street, Chengguan District, Lanzhou, 730000, People’s Republic of China, Email [email protected]: Chronic obstructive pulmonary disease (COPD) and lung cancer frequently coexist, constituting a clinically consequential comorbidity with major implications for precision medicine.Mechanistic Insights: Beyond shared environmental exposures such as tobacco smoke and air pollution, COPD has emerged as an independent driver of pulmonary carcinogenesis, mediated through persistent inflammation, genomic instability, epigenetic remodeling, and microbiome–immune dysregulation. Patients with COPD-associated lung cancer exhibit distinct molecular hallmarks, including reduced EGFR mutation frequency, enrichment of LRP1B truncations, and elevated tumor mutational burden, which collectively reprogram tumor immunogenicity and therapeutic responsiveness, favoring immune checkpoint blockade over targeted EGFR-directed therapy.Diagnostic and Preventive Strategies: Recent advances integrating low-dose CT (LDCT) with spirometry, liquid biomarkers (eg, S100A12, TLR4), and AI-enhanced radiomic algorithms have substantially improved early detection capabilities. In parallel, microbiome-derived signatures provide novel tools for risk stratification and treatment personalization.Therapeutic Implications: Preventive and therapeutic strategies, including statin therapy, inhaled corticosteroids, preoperative pulmonary optimization, and microbiome modulation, are emerging as promising approaches to intercept the COPD–lung cancer continuum and improve clinical outcomes.Conclusion: This review synthesizes current evidence spanning epidemiology, molecular pathogenesis, diagnostic innovations, and comorbidity-tailored interventions, culminating in a “comorbidity-centered precision management” framework. By bridging mechanistic discoveries with clinical implementation, this paradigm may contribute to reducing COPD–lung cancer mortality and could support the advancement of the global precision oncology agenda.Keywords: COPD–lung cancer comorbidity, precision medicine, immunotherapy, microbiome biomarkers, molecular pathogenesis, early detection