Cancer cells and tissues often have high metabolic rates. this may result in a demand for oxygen and nutrients exceeding the supply. As a result these tissues are characterized by the presence of hypoxia which is also the primary factor controlling angiogenesis. Under hypoxic conditions, hypoxia inducible factor binds to the hypoxia response element present in the VEGF gene, thus inducing the transcription of VEGF protein. Circulating VEGF binds to VEGF receptor (VEGFR)-1 and VEGFR-2 and to its coreceptors neuropilin (NRP)-1 and NRP-2 with high binding affinity . These receptors are expressed on the surface of endothelial cells, and they play a critical role in the development of angiogenesis by stimulating the recruitment and proliferation of endothelial cells.
Bevacizumab acts by selectively binding circulating VEGF, thereby inhibiting the binding of VEGF to its cell surface receptors. This inhibition leads to a reduction in microvascular growth of tumor blood vessels and thus limits the blood supply to tumor tissues. These effects also lower tissue interstitial pressure increase vascular permeability, may increase delivery of chemotherapeutic agents, and favor apoptosis of tumor endothelial cells.
