LAUSR

Simple Summary Melanoma is the most aggressive and potentially lethal form of skin cancer. Research over recent decades has highlighted the role of tumour vasculature in altering the metabolic function of cancer cells, infiltration of immune cells, and cancer cell dissemination. However, variations in the modes of vessel formation in melanoma have made this process difficult to target. In particular, the role of endothelial progenitor cells in melanoma vascularization-promoting vasculogenesis begins to be understood. Progenitor recruitment, vessel formation, and paracrine activity are among the steps contributing to tumour metastasis and affecting the impact of anti-angiogenic drugs, as detailed in this review. Abstract The aggressiveness of solid cancers, such as melanoma, relies on their metastatic potential. It has become evident that this key cause of mortality is largely conferred by the tumour-associated stromal cells, especially endothelial cells. In addition to their essential role in the formation of the tumour vasculature, endothelial cells significantly contribute to the establishment of the tumour microenvironment, thus enabling the dissemination of cancer cells. Melanoma tumour vascularization occurs through diverse biological processes. Vasculogenesis is the formation of de novo blood vessels from endothelial progenitor cells (EPCs), and recent research has shown the role of EPCs in melanoma tumour vascularization. A more detailed understanding of the complex role of EPCs and how they contribute to the abnormal vessel structures in tumours is of importance. Moreover, anti-angiogenic drugs have a limited effect on melanoma tumour vascularization, and the role of these drugs on EPCs remains to be clarified. Overall, targeting cancer vasculature remains a challenge, and the role of anti-angiogenic drugs and combination therapies in melanoma, a focus of this review, is an area of extensive exploration.