Bevacizumab is the first anti-angiogenic agent approved for the treatment of metastatic colorectal cancer. The need for patient selection before initiating therapy necessitates the study of various proteins expressed in metastatic colorectal cancer tissue as candidate predictive markers. Immunohistochemistry is a valuable, commonly available and cost-effective method to assess predictive biomarkers. However, it is subject to variations and therefore requires rigorous protocol standardizations. Furthermore, validated quantification methodologies to study these angiogenic elements have to be applied. Based on their function in tumor angiogenesis and their relation to the mechanism of action of bevacizumab, protein markers were divided in four groups: VEGF A-signaling proteins; other relevant angiogenesis factors; factors regarding the tumor microenvironment and tumor intrinsic markers. Conceivably, nimbly selecting a small but relevant group of therapy-guided patients by the appropriate combination of predictive biomarkers may confer great value to this angiogenic inhibitor.
Keywords: Avastin®; VEGF inhibitor; anti-angiogenesis; bevacizumab; immunohistochemistry; metastatic colorectal cancer; predictive biomarker.