Advances in targeting vasculogenic mimicry in malignant tumors using monomeric compounds from Traditional Chinese...

Vasculogenic mimicry (VM), a pivotal mechanism underlying tumor resistance to anti-angiogenic therapies, presents key challenges in oncology treatment. Chinese herbal monomers exhibit notable therapeutic potential in cancer treatment, particularly regarding their capacity to inhibit tumor VM formation. However, to the best of our knowledge, no comprehensive literature review has systematically explored the specific molecular mechanisms through which Chinese herbal monomers exert their anti-VM effects in tumor cells, to date. Therefore, the present systematic review evaluates the therapeutic potential of 46 natural monomers derived from Traditional Chinese Medicine (TCM) across 16 cancer types, through a comprehensive analysis of 64 preclinical studies. TCM monomers inhibit VM formation by modulating key signaling pathways (PI3K/AKT, MAPK and Notch) and downregulating key molecular markers (vascular endothelial-cadherin, MMPs and hypoxia inducible factor-1α). The identified compounds exhibit multi-target regulatory capabilities through epithelial-mesenchymal transition suppression, matrix metalloproteinase inhibition and angiogenesis-related signaling pathway modulation. These findings elucidate the mechanistic basis for the anti-VM effects of TCM and propose a novel therapeutic avenue to potentially overcome resistance in malignant tumors, highlighting the translational value of phytochemical-based combination therapies in precision oncology.