“…Tumor progression may be promoted by both chronic (diffusion-limited) as well as acute (fluctuating) tumor hypoxia (Janssen et al, 2005;Rofstad et al, 2007), and antiangiogenic therapy increases the proportion of cells undergoing both types of hypoxia (Rofstad et al, 2007). Currently, intervention with antiangiogenic agents is performed in relatively late stages of disease, where there are more angiogenic and survival pathways involved and manipulations of any single factor (such as inhibition of vascular endothelial growth factor) likely become less critical for cancer progression Kerbel and Folkman, 2002;Franco et al, 2006). Interestingly, addition of bevacizumab to first-line chemotherapy in patients with metastatic colorectal cancer increased response rates and prolonged overall survival (Hurwitz et al, 2004).…”