Exosomes and lung cancer: Biogenesis, pathogenic mechanisms, biomarkers, and therapeutic applications

Lung cancer remains a global health crisis characterized by high mortality rates and pervasive therapeutic resistance. Recent advances in molecular oncology have identified exosomes, nanoscale extracellular vesicles with diameters of 30–150 nm, as pivotal mediators of the lateral transmission of bioactive molecular signals. This review provides a high-level synthesis of exosomal biogenesis and the nuanced roles these vesicles play in lung cancer. Specifically, we discuss how tumor-derived exosomes orchestrate remodeling of the tumor microenvironment, facilitate premetastatic niche formation, and drive immune evasion via the programmed death-1/programmed death-ligand 1 axis and recruitment of regulatory cells. A significant portion of this review is dedicated to exosomal noncoding RNAs, including microRNAs, long noncoding RNAs, and circular RNAs, emphasizing their stability as liquid biopsy substrates and their involvement in cross-resistance to tyrosine kinase inhibitors and immunotherapies. Furthermore, we evaluate the transition of exosomes from diagnostic candidates to therapeutic tools, including their utility as bio-inspired drug delivery systems and cancer vaccines. Finally, this narrative review critically examines the technical hurdles, ranging from standardized isolation methods to good manufacturing practice scalability that must be overcome to integrate exosome-based precision medicine into routine clinical management of patients with lung cancer.