Tumor's Own Blood Supply: Decoding Vasculogenic Mimicry through Hypoxia, EMT, and Epigenetics

Tumor growth and progression depend on adequate blood supply, which is traditionally maintained through sprouting angiogenesis. However, an alternative form of vascular formation, termed vasculogenic mimicry (VM), has been identified in various tumors. A growing body of evidence suggests that VM is closely associated with tumor invasion, metastasis, and poor clinical outcomes in malignancies. Despite its significance, the precise molecular mechanisms underlying VM remain poorly understood. Recent studies have implicated multiple factors, including the tumor microenvironment, epithelial-mesenchymal transition, and epigenetics, in the regulation of this process. Although numerous anti-angiogenic therapies have been developed and achieved clinical success to some extent, certain limitations persist. This review aims to provide a comprehensive overview of the pathological mechanisms, diagnostic methods, potential clinical applications, and existing challenges associated with tumor VM.