Monitoring of tumor vascular normalization: the key points from basic research to clinical application

Tumor vascular normalization alleviates hypoxia in the tumor microenvironment, reduces the degree of malignancy, and increases the efficacy of traditional therapy. However, the time window for vascular normalization is narrow; therefore, how to determine the initial and final points of the time window accurately is a key factor in combination therapy. At present, the gold standard for detecting the normalization of tumor blood vessels is histological staining, including tumor perfusion, microvessel density (MVD), vascular morphology, and permeability. However, this detection method is almost unrepeatable in the same individual and does not dynamically monitor the trend of the time window; therefore, finding a relatively simple and specific monitoring index has important clinical significance. Imaging has long been used to assess changes in tumor blood vessels and tumor changes caused by the oxygen environment in clinical practice; some preclinical and clinical research studies demonstrate the feasibility to assess vascular changes, and some new methods were in preclinical research. In this review, we update the most recent insights of evaluating tumor vascular normalization.