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Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis in embryonic development, skeletal growth, and reproductive function and has been implicated in pathological angiogenesis associated with tumors, intraocular neovascular diseases, and other diseases. Despite its discovery in 1983, VEGF still ranks among the top five after Her-2, EGFR, CD3E, and CD19 according to the Pharma Projects database. Over the past two decades, the critical role of VEGF in the regulation of physiological and pathological angiogenesis has been elucidated, resulting in VEGF becoming an ‘inspiring’ target for both current and innovative drugs.
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VEGF Family: Ligands and Receptors
To fully appreciate the implications and potential of VEGF as a drug target, understanding the various roles of VEGF in physiologic processes is critical. The VEGF signaling system is complex, covering five major subtypes: VEGF-A, VEGF-B, VEGF-C, VEGF-D, placental growth factor (PIGF) with three tyrosine kinase receptors, VEGFR-1, VEGFR-2, and VEGFR-3.
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The Role of VEGF in Tumors
Along with other growth factors produced by the tumor, VEGF causes an “angiogenic switch” to be turned on resulting in new blood vessel formation around the tumor and enabling exponential growth. Due to the abnormal increase in angiogenesis, the resulting blood vessels formed are irregular in shape, curved, and do not form venules, arterioles, and capillaries. The poor performances of these abnormal vessels result in poor blood flow, exacerbating hypoxia that results in further VEGF production and subsequently, angiogenesis.
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Representative Drugs Targeting VEGF in Progress
The central role that VEGF plays in tumor angiogenesis makes it an effective target for antitumor therapy. Currently, an increasing number of companies are focusing on VEGF-targeted antibody drugs including monoclonal and bispecific antibodies (bsAb).
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