Pro-angiogenic growth factor signaling

Pro-angiogenic growth factor signaling refers to the complex network of biochemical pathways that stimulate the formation of new blood vessels from pre-existing ones, a process known as angiogenesis [1]. This signaling is primarily mediated by growth factors such as Vascular Endothelial Growth Factor (VEGF), Fibroblast Growth Factor (FGF), and Platelet-Derived Growth Factor (PDGF) binding to their respective receptor tyrosine kinases on endothelial cells [3, 4]. Upon ligand binding, these receptors undergo dimerization and autophosphorylation, triggering downstream pathways such as PI3K/Akt and MAPK/ERK that promote cell survival, proliferation, and migration [4]. In healthy tissues, this process is tightly regulated and essential for development and wound repair; however, in pathological states like cancer, tumors hijack these pathways to ensure a blood supply for growth and metastasis [2]. Therapeutic intervention typically involves monoclonal antibodies that sequester ligands or small-molecule inhibitors that block receptor kinase activity, thereby inhibiting vessel growth and starving the tumor [1, 3]. Beyond oncology, targeting these pathways is also a standard of care for neovascular ocular diseases like age-related macular degeneration, where excessive vessel growth leads to vision loss [1].

Other names

Angiogenesis signaling pathwayPro-angiogenic signaling cascadeVEGF/FGF/PDGF signalingTumor angiogenesis pathway

Drugs targeting this signaling pathway primarily act by either sequestering pro-angiogenic ligands (e.g., VEGF-A) to prevent receptor binding or by inhibiting the intracellular kinase domains of receptor tyrosine kinases (e.g., VEGFR, FGFR, PDGFR) to block downstream signal transduction [1, 2].