Bridging Inflammation and Oncology: The Role and Therapeutic Potential of Macrophage Migration Inhibitory Factor in Lung Cancer

Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for more deaths than any other ma-lignancy. Despite advances in treatment, it remains highly lethal, with 5-year survival rates showing minimal improve-ment over the past several decades, highlighting a critical unmet clinical need. Macrophage Migration Inhibitory Factor (MIF) is a multifunctional cytokine that contributes to inflammation and cancer, promoting tumor growth, progression, and metastasis through modulation of the tumor microenvironment, stimulation of angiogenesis, and regulation of im-mune responses. Polymorphisms in the promoter region of MIF, such as high-expression CATT repeats, influence MIF expression and susceptibility to a range of inflammatory, autoimmune, and malignant disorders, yet their role in lung cancer remains largely unexplored. Therapeutic strategies targeting MIF, including small-molecule inhibitors, antibod-ies, and peptide-based agents, have shown promise in preclinical models, although their clinical translation is still lim-ited. This review discusses the dual role of MIF in inflammation and oncology, summarizes current therapeutic devel-opments, and emphasizes the potential of MIF-targeted interventions in lung cancer. It discusses the significance of ge-netic predisposition, particularly high-expression MIF alleles, in guiding personalized treatment strategies for lung can-cer and optimizing clinical outcomes in patients most likely to benefit from MIF inhibition.