Vascular Endothelial Growth Factor Receptor 1, a Therapeutic Target in Cancer, Inflammation and Other Disorders

The vascular endothelial growth factor (VEGF)/VEGF receptor pathways are essential for the regulation of angiogenesis during embryonic development and tumor progression. VEGF receptor 1 (VEGFR-1) has been shown to promote tumor growth and metastasis through the regulation of multiple biological functions in cancer cells, vasculature, stroma and other tumor-associated cells. VEGFR-1 signaling is required for the survival of endothelial cells and macrophages and the mobilization of cancer cells, endothelial cells, myeloid progenitors, and monocyte/macrophages. VEGFR-1 was reported to have a function in eliciting epithelial-to-mesenchymal transition in cancer cells toward invasive and metastatic phenotype. Furthermore, VEGFR-1 was found to promote metastasis through initiating pre-metastatic niche by VEGFR-1 positive bone marrow progenitors. It was reported that VEGFR-1 had an active role in promoting inflammation through modulating immune cells and mediating immunosuppression by VEGFR-1 positive myeloid cells. Given that VEGFR-1 has a multi-functional role in promoting angiogenesis, inflammation, tumor growth and metastasis, VEGFR-1 has emerged as a promising therapeutic target for treatment of cancer as well as angiogenesis and inflammation associated disorders.