Vascular endothelial growth factor receptor and platelet-derived growth factor receptor signaling pathways (VEGFR/PDGFR pathways)

The Vascular Endothelial Growth Factor Receptor (VEGFR) and Platelet-Derived Growth Factor Receptor (PDGFR) signaling pathways are essential mediators of vascular development and tissue homeostasis. VEGFR signaling, particularly through VEGFR-2, is the primary driver of angiogenesis, promoting the proliferation, migration, and survival of endothelial cells [1, 3, 5]. PDGFR signaling plays a complementary role by regulating the recruitment of pericytes and smooth muscle cells, which are necessary for vessel maturation and stabilization [4, 11]. In pathological states such as cancer, these pathways are frequently overactivated to facilitate tumor-associated neovascularization, providing the blood supply required for tumor growth and metastasis [2, 8, 9]. Consequently, multi-kinase inhibitors that target both VEGFR and PDGFR are widely used in oncology to disrupt the tumor vasculature and inhibit disease progression [5, 7, 8]. These pathways are also significant in the pathogenesis of fibrotic diseases, where PDGFR drives fibroblast activation, and in ocular disorders like age-related macular degeneration, where excessive VEGF leads to vision-threatening leaky vessels [4, 9]. Recent research also highlights cross-family signaling, where PDGF ligands can activate VEGFRs, potentially contributing to drug resistance in anti-angiogenic therapies [10, 12].

Other names

VEGF/PDGF signaling axisAngiogenic growth factor signalingReceptor tyrosine kinase class III and IV signalingVEGF-PDGF pathway crosstalk

Inhibition of the intracellular tyrosine kinase domain of VEGFR and PDGFR, which prevents ATP binding and subsequent autophosphorylation, thereby blocking downstream signaling cascades such as the MAPK/ERK, PI3K/Akt, and PLCγ pathways.