Vascular co‐option and vasculogenic mimicry mediate resistance to antiangiogenic strategies

Background The concept that all the tumors need the formation of new vessels to grow inspired the hypothesis that inhibition of angiogenesis would have led to “cure” cancer. The expectancy that this type of therapy would have avoided the insurgence of resistance was based on the concept that targeting normal vessels, instead of the cancer cells which easily develop new mutations, would have allowed evasion of drug caused selection is, however, more complex as it was made apparent by the discovery of nonangiogenic tumors. At the same time an increasing number of trials with antiangiogenic drugs were coming out as not as successful as expected, mostly because of the appearance of unexpected resistance. Recent Findings Among the several different mechanisms of resistance to antiangiogenic treatment by now described, we review the evidences that vascular co‐option and vasculogenic mimicry by nonangiogenic tumors are effectively two of such mechanisms. We focused on reviewing exclusively the study, both clinical and preclinical, that offer a demonstration that vascular co‐option and vasculogenic mimicry are effectively two mechanisms of both intrinsic and acquired resistance. Conclusion The discovery that vascular co‐opting and vasculogenic mimicry are two ways of escaping antiangiogenic treatment, prompts the need for a better understanding of this phenomenon in order to improve cancer treatment.