Vascular endothelial growth factor receptor 3 (VEGFR-3) (VEGFR-3)

Vascular endothelial growth factor receptor 3 (VEGFR-3), encoded by the FLT4 gene, is a transmembrane receptor tyrosine kinase that serves as a master regulator of the lymphatic system's development and maintenance [1, 3, 4]. It is primarily activated by its ligands, VEGF-C and VEGF-D, which trigger intracellular signaling pathways such as MAPK/ERK and PI3K/AKT to promote the proliferation, migration, and survival of lymphatic endothelial cells [1, 6, 13]. Beyond its role in lymphangiogenesis, VEGFR-3 is involved in blood vessel remodeling and angiogenesis, particularly during embryonic development and in pathological states like retinal neovascularization [15, 17]. In oncology, the overexpression of VEGFR-3 in tumor-associated lymphatic vessels facilitates the spread of cancer cells to regional lymph nodes, making it a key target for anti-metastatic therapies [4, 12]. Genetic mutations in the FLT4 gene are the primary cause of Milroy disease, a hereditary form of lymphedema, and are also associated with congenital heart conditions like Tetralogy of Fallot [1, 8, 14]. Several small-molecule multikinase inhibitors, including sorafenib, sunitinib, and pazopanib, target VEGFR-3 to disrupt tumor-associated lymphangiogenesis and vascularization [10, 12]. Monitoring FLT4 gene amplification or expression levels of its ligands can serve as potential biomarkers for predicting disease progression or response to anti-angiogenic treatments [12, 13].

Other names

Fms-related tyrosine kinase 4FLT4VEGFR3PCLLMPH1ALMPHM1CHTD7Tyrosine-protein kinase receptor FLT4

Inhibition of the receptor tyrosine kinase activity, blocking downstream signaling pathways (e.g., MAPK/ERK and PI3K/AKT) activated by VEGF-C and VEGF-D [1, 5, 10, 13].