The mechanisms of action and targeting potential of vasculogenic mimicry in breast cancer metastasis

Vasculogenic Mimicry (VM) is a distinct mode of tumor vascularization, separate from angiogenesis, whereby highly invasive cancer cells form functional vascular-like structures to facilitate the transport of blood and tumor cells. Unlike angiogenesis, which is mediated by endothelial cells, VM is exclusively driven by cancer cells and is recognized as a pivotal mechanism in breast cancer progression. This review is designed to elucidate the cellular and molecular mechanisms underpinning VM in breast cancer metastasis, with emphasis placed on the contributions of the tumor microenvironment, epithelial-mesenchymal transition (EMT), and cancer stem cells (CSCs). The involvement of key signaling pathways, such as EphA2/PIK3R1/CTNNB1, is also examined. Furthermore, the role of VM in promoting tumor growth, invasion, and distant metastasis is analyzed, alongside its contribution to resistance against established anti-angiogenic therapies. The therapeutic potential of targeting VM is explored, encompassing the development of specific inhibitors and combination therapy strategies. Additionally, the utility of VM as a prognostic and predictive marker in breast cancer is evaluated, and future research directions, along with challenges in clinical translation, are outlined.