Glioblastoma vasculogenic mimicry: signaling pathways progression and potential anti-angiogenesis targets

Glioblastoma (GBM) is a highly angiogenic malignancy that is resistant to standard therapy; neo-formed vessels of this aggressive malignancy are thought to arise by sprouting of pre-existing brain capillaries. However, the conventional anti-angiogenic therapy, which seemed promising initially, shows transitory and incomplete efficacy. The discovery of vasculogenic mimicry (VM) has offered a new horizon for understanding tumor vascularization. VM is a tumor cell-constituted, matrix-embedded fluid-conducting meshwork that is independent of endothelial cells and is positively correlated with poor prognosis. Therefore, a better understanding of GBM vasculature is needed to optimize anti-angiogenic therapy. This review focuses on the signaling molecules and cascades involved in VM in relation to ongoing glioma research, as well as the clinical translational advances in GBM that have been offered by the development of optimized anti-angiogenesis treatment modalities.