Exploring the mechanism of volatile organic compounds in respiratory tract tumors based on network toxicology and molecular simulation.

This study elucidates the pathogenic role of environmental volatile organic compounds (VOCs) in respiratory tumorigenesis, focusing on head and neck cancer (HNSC), lung squamous cell carcinoma (LUSC), and lung adenocarcinoma (LUAD). As pervasive pollutants derived from industrial emissions, traffic exhaust, and indoor contaminants, VOCs threaten public health, yet their molecular mechanisms in multi-cancer pathogenesis remain poorly defined. By integrating network toxicology and molecular docking, we systematically dissected VOC-driven disruptions in respiratory homeostasis. Disease-associated targets were mined from TCGA, CTD, and GeneCards databases, followed by core target identification via STRING network analysis and Cytoscape. Functional enrichment (GO/KEGG) and survival analyses revealed critical pathways, while molecular docking and molecular dynamics validated pollutant-target interactions. Our results demonstrate that VOCs directly perturb key targets (FN1, PECAM1, CDK1 etc.), hijacking PI3K-Akt signaling, ECM-receptor interactions, and cell cycle regulation to promote apoptosis evasion and unchecked proliferation. High-affinity binding between VOCs and targets underscores their role as environmental carcinogens. Strikingly, shared dysregulated pathway across HNSC, LUSC, and LUAD highlight pan-respiratory susceptibility to VOC exposure. Epidemiological correlations align with molecular findings, emphasizing cumulative risks in populations exposed to air pollution. The study also highlights FN1 and PECAM1 as key targets, emphasizing the importance of these markers in VOC-associated carcinogenesis.