Role of bevacizumab in colorectal cancer growth and its adverse effects: a review

Abstract

Angiogenesis affects both wound healing and malignant cell growth through nutrients and oxygen. Vascular endothelial growth factor (VEGF) is the most important element involved in this complex process. Inhibition of VEGF influences angiogenesis and may restrict tumor growth and metastatic ability. Modern anti-angiogenic therapy is based on this theory. Bevacizumab is a recombinant humanized monoclonal antibody (immunoglobulin G1) which binds with VEGF-A forming a large molecule. It can not be bound with VEGF tyrosine kinase receptors preventing VEGF-A incorporation; thus its activity is inhibited inducing blockage of VEGF-mediated angiogenesis. Bevacizumab, in combination with chemotherapy or other novel targeted therapeutic agents, is currently used more frequently in clinical practice, mainly for managing advanced colorectal cancer. It is also used for managing other malignancies, such as breast cancer, pancreatic cancer, prostate cancer, non small-cell lung cancer, metastatic renal carcinoma and ovarian tumors. Although it is generally considered a safe treatment, there are reports of some rare side effects which should be taken into account. Recent experiments in rats and mice show promising results with a wider therapeutic range.

Keywords: Angiogenesis; Anti-angiogenic agents; Avastin; Bevacizumab; Cancer targeted therapy; Colorectal cancer; Vascular endothelial growth factor.

Figure 1

The process of angiogenesis and the mechanism of action of bevacizumab. A: The malignant cells secrete vascular endothelial growth factor (VEGF)-A; B: It is incorporated with its tyrosine kinase receptors (VEGFRs), promoting endothelial cell proliferation and migration; C: It leads to increased angiogenesis inducing tumor growth; D: Bevacizumab is combined with VEGF-A forming a new large molecule that lacks the ability to bind with its receptors; thus avoiding its incorporation and action, it then inhibits angiogenesis. Taken from Shord et al[15].