Vascular endothelial growth factor and fibroblast growth factor signaling pathways (VEGF/FGF pathways)

The VEGF/FGF-related pathways represent a critical signaling network that governs angiogenesis, lymphangiogenesis, and cellular homeostasis. The Vascular Endothelial Growth Factor (VEGF) family is the primary driver of physiological and pathological blood vessel formation, while the Fibroblast Growth Factor (FGF) family plays a complementary role in promoting endothelial cell survival and tissue repair (Source: Nature Medicine, 2016; PubMed: 27149218). In oncology, these pathways are frequently co-activated, with FGF signaling often serving as a key escape mechanism that confers resistance to selective anti-VEGF therapies (Source: Cancer Cell, 2005; PubMed: 16286018). Consequently, the dual inhibition of VEGFR and FGFR has emerged as a potent therapeutic strategy to achieve more durable suppression of tumor vascularization and growth. Beyond cancer, these pathways are central to the pathogenesis of exudative eye diseases, such as age-related macular degeneration, where abnormal vessel growth leads to vision loss. Clinical management of drugs targeting these pathways is complex due to systemic side effects like hypertension and impaired wound healing, which result from the inhibition of physiological angiogenesis. This entry is flagged as 'incorrect' because it describes a broad signaling axis rather than a single molecular target.

Other names

VEGFR/FGFR signaling axisAngiogenic growth factor pathwaysVEGF and FGF signalingPro-angiogenic pathways

Small molecule inhibitors competitively bind to the adenosine triphosphate (ATP) binding site of the intracellular tyrosine kinase domains of Vascular Endothelial Growth Factor Receptors (VEGFR1-3) and Fibroblast Growth Factor Receptors (FGFR1-4). This inhibition prevents receptor autophosphorylation and blocks the activation of downstream signaling cascades, such as the RAS/MAPK and PI3K/Akt pathways, which are essential for endothelial cell survival and proliferation (Source: Nature Reviews Cancer, 2010; PubMed: 20651738).