Vascular adhesion protein-1 (VAP-1) in cancer: mechanisms and translational implications for diagnosis, prognosis, and therapy

Vascular adhesion protein-1 (VAP-1), also known as amine oxidase copper-containing 3 (AOC3), is a multifunctional molecule with dual adhesive and enzymatic activities, and can regulate leukocyte trafficking, redox signaling, and stromal interactions within the tumor microenvironment. Evidence from both experimental and clinical investigations has demonstrated the aberrant expression of VAP-1 in a wide range of cancers and its correlation with tumor progression and outcomes. Elevated tissue levels of VAP-1 are generally associated with aggressive behavior and unfavorable survival in gliomas and breast, colorectal, and ovarian cancers, whereas altered circulating levels in gastric and thyroid cancers may have adjunctive diagnostic relevance when interpreted alongside conventional biomarkers, imaging findings, and clinicopathological features. Preclinical studies have documented the therapeutic advantages of VAP-1, as the inhibition of its enzymatic activities can suppress angiogenesis, reduce the infiltration of immunosuppressive myeloid cells, and restore antitumor immunity, with synergy observed in combination with immune checkpoint inhibitors. Moreover, novel molecular imaging strategies using VAP-1-specific ligands may support theranostic applications, offering opportunities for patient stratification and real-time assessment of therapeutic responses in selected contexts. This review gathers evidence on the involvement of VAP-1 in the pathogenesis of cancers and its diagnostic and therapeutic applications. The integration of data from basic and translational studies will underscore both the opportunities and challenges of targeting VAP-1 and guide future studies of the applications of targeting VAP-1 in the clinical setting.