Molecular Mechanisms of Vasculogenesis in Human Cancers: From Developmental Pathways to Tumor Vascular Remodeling and Therapeutic Targeting

Vasculogenesis, the de novo formation of blood vessels from endothelial progenitor cells, is increasingly recognized as a critical contributor to tumor vascularization, complementing classical angiogenesis and promoting cancer progression, metastasis, therapeutic resistance, and disease recurrence. This narrative review aims to provide a comprehensive overview of the molecular mechanisms governing vasculogenesis across human malignancies and to discuss their translational relevance for targeted cancer therapy. This is a narrative, mechanistically oriented review rather than a systematic review or meta-analysis. The literature was searched in PubMed, Scopus, and Google Scholar, with the primary search covering publications from January 2010 to February 2026, while seminal earlier studies were included when they established fundamental concepts in vascular biology. Search terms included combinations of “vasculogenesis”, “tumor vasculogenesis”, “angiogenesis”, “endothelial progenitor cells”, “vascular remodeling”, “VEGF”, “HIF-1α”, “Notch”, “Wnt”, “PI3K/AKT”, “TGF-β”, “EndMT”, “mechanotransduction”, “non-coding RNAs”, “tumor microenvironment”, and “cancer”. Evidence was qualitatively appraised and synthesized according to mechanistic relevance and consistency across experimental and clinical studies. The reviewed literature highlights the complex interplay between developmental signaling pathways, endothelial plasticity, mechanical cues, inflammatory mediators, and non-coding RNAs in regulating tumor vasculogenesis. Collectively, these findings suggest that targeting vasculogenesis-related pathways may complement existing anti-angiogenic therapies and represent a promising strategy for improving precision oncology and overcoming treatment resistance.