The growth of tumors is dependent on the recruitment of new blood vessels. This process, termed angiogenesis, does not occur in normal adult tissues except in the context of wound repair, tissue remodeling, or inflammation. Under normal circumstances, the process of angiogenesis is highly regulated, and involves a number of steps. In tumors, angiogenesis often proceeds in a disorderly fashion, resulting in the development of leaky, tortuous, excessively branching blood vessels. The resulting microcirculation is inefficient, resulting in tumor tissue conditions that hamper the ability of chemotherapeutic agents to diffuse into the target cells.

VEGF in CRC

The process of angiogenesis is regulated by a number of growth factors including vascular endothelial growth factor (VEGF). VEGF is secreted by tumor cells and stromal cells, and acts by binding to receptors on the surface of endothelial cells. Activation of these receptors initiates a number of intracellular signaling cascades that increase endothelial cell survival, proliferation, migration, and differentiation. Increased VEGF expression appears to play a role in the development of metastases since the overexpression of VEGF correlates with tumor progression and a worsening prognosis in patients with CRC.