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Targeting angiogenesis:
Inhibition of a tumor’s lifeline

Angiogenesis is a vital process that facilitates tumor growth and survival.^1-3 Tumor angiogenesis refers to the ability of a tumor to stimulate new blood vessel formation.^1,2 This critical step in development enables tumor expansion, local invasion, and dissemination through^1-3:

• Delivery of oxygen, nutrients, and survival factors

• Production of growth factors that benefit tumor cells

• Formation of a route for tumor cell egress

Angiogenesis is a well-controlled process that is regulated by angiogenic, growth, and survival factors that are secreted by the malignant cells as well as other cells within the tumor microenvironment.^2,4

Pro-angiogenic factors, including VEGF, bind to receptors on the vascular endothelial cells of nearby blood vessels and promote cell proliferation, migration, and invasion into the tumor.^1,2,5,6 These receptors include VEGF receptor 2 (VEGFR2) and neuropilin-1 (NRP1), a transmembrane receptor expressed on vascular endothelial cells that plays an important role in angiogenic signaling.^5-8 NRP1 is expressed on the vasculature of multiple tumor types and NRP1-mediated signaling may promote vascular maturation, a critical step in angiogenesis.^7-9

The process of sprouting angiogenesis is regulated by many extracellular factors, including EGF-like domain-containing protein 7 (EGFL7), a protein expressed by endothelial cells.^10-13 EGFL7 is associated with the extracellular matrix and is upregulated in many proliferative tissues, including tumors.^11-13 EGFL7 supports endothelial cell adhesion and vascular tube formation by defining an efficient migratory path for endothelial cells.¹³ Furthermore, it also protects endothelial cells that are under biological stress, another pro-survival mechanism.¹⁴

Next: Anti-NRP1