VEGFR2 (KDR/Flk-1) on vascular endothelial cells

Class

Recombinant human endostatin (angiogenesis inhibitor)

Pathway

anti-angiogenesis via blockade of VEGF-induced KDR/flk-1 phosphorylation and inhibition of Wnt/beta-catenin signaling

VEGFR2, also called KDR or Flk-1, is a receptor tyrosine kinase found on the surface of vascular endothelial cells, the cells that line blood vessels. When the growth factor VEGF binds this receptor, it triggers autophosphorylation and downstream signaling that drives endothelial cell proliferation, migration, and the formation of new blood vessels, a process called angiogenesis. Tumors depend on angiogenesis to obtain oxygen and nutrients beyond a small initial size, and abnormal new vessel growth also contributes to certain eye diseases and other pathological conditions. Blocking VEGFR2 signaling, either by preventing VEGF from binding the receptor or by inhibiting downstream phosphorylation events, interrupts this vessel-building program and can slow tumor growth or limit pathological vascular proliferation. Agents that act on this mechanism include monoclonal antibodies against VEGF or VEGFR2 as well as small molecules and biologic inhibitors that interfere with the pathway more broadly. Recombinant endostatin, a naturally occurring anti-angiogenic protein fragment, is one such agent; it works by dampening VEGF-induced receptor activation and by additionally modulating other growth-related signaling, giving it a broader anti-angiogenic footprint than an agent that blocks a single step in the pathway.