Pro-angiogenic signaling pathways in tumor vasculature

Pro-angiogenic signaling pathways in tumor vasculature represent the network of molecular interactions that stimulate the growth of new blood vessels to support tumor expansion and metastasis [1]. The primary mediator is the Vascular Endothelial Growth Factor (VEGF) family, which binds to receptor tyrosine kinases (VEGFR-1, -2, and -3) on endothelial cells to promote survival, proliferation, and migration [2]. Other significant contributors include the Angiopoietin-Tie2 pathway, which regulates vessel maturation, and the Notch signaling pathway, which coordinates tip and stalk cell differentiation during sprouting [3]. In many cancers, these pathways are constitutively active due to hypoxia-induced factors (HIFs) or oncogenic mutations, leading to a disorganized and leaky vascular network [1]. Therapeutic agents targeting these pathways include monoclonal antibodies like bevacizumab, which neutralizes VEGF-A, and small-molecule inhibitors like sunitinib that block VEGFR signaling [4]. While these treatments can inhibit tumor growth and improve progression-free survival, they are often associated with systemic side effects such as hypertension and proteinuria due to the inhibition of physiological angiogenesis in healthy tissues [2].

Other names

Tumor angiogenesis signalingNeovascularization pathwaysVEGF-mediated signalingAngiogenic switch

Inhibition of pro-angiogenic ligands (e.g., VEGF-A) or their corresponding receptor tyrosine kinases (e.g., VEGFR2) to prevent endothelial cell activation and vessel formation.