Benefits and Pitfalls of Tumor Vessel Normalization

Tumor vasculature has been intensively studied not only to understand its role in tumor progression and metastasis but also to discover regulatory pro- and anti-angiogenic molecules and cells. Until now, numerous anti-angiogenic agents have been developed, with more than ten agents currently being administered or tested to treat patients with various types of cancers. Despite high hopes for success, recent clinical trials have shown that these anti-angiogenic agents are not as effective as other drugs with different targets in terms of increasing patient survival when used as a single agent. These unsuccessful trials have led researchers to reevaluate the nature of tumor vasculature and the dynamic consequences that arise from anti-angiogenic treatments. Subsequently, a new hypothesis was introduced, where tumor vessels were sought to be tamed and harnessed to our advantage rather than simply attempting to eliminate them, which, by itself, has shown only marginal survival benefit. Thus, a new avenue of research was revealed, and the concept "tumor vessel normalization" has gained considerable attention ever since. However, our knowledge in this field is still rather rudimentary, and much still needs to be accomplished in order to overcome the pitfalls and relish the benefits of normalizing tumor vessels for anticancer therapy.