When tumors are (co-)opting to resist anti-angiogenic treatment

The role of angiogenesis, i.e., the growth of new blood vessels, in tumor biology revolutionized targeted cancer therapy when it was introduced approximately 10–15 years ago (1). Today, however, we know that anti-angiogenic treatment with either antibodies or small molecular inhibitors of the vascular endothelial growth factor (VEGF)-A—VEGF receptor (VEGFR)-2 axis are less effective in most malignant indications than initially expected (2). Such agents are, however, very effective at blocking tumor growth in most pre-clinical models, due to their potent effects on regressing the tumor vasculature leading to tumor hypoxia and necrosis.