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This is in line with other preclinical studies which have linked vascular normalization to an enhanced efficacy of radiation treatment [13, 27].
At the same time, it has been shown that the vascular normalization occurs only transiently and that continuation of angiostatic treatment eventually causes vessel regression and reduced tumor oxygenation [22, 31, 34].
For example, our previous work has focussed on the role of galectins in tumor angiogenesis and cancer [35–40].
This was instigated by our discovery of galectin-1 as a pro-angiogenic factor that is essential for endothelial cell function during tumor angiogenesis [41–44].
The mechanisms by which angiostatic drugs improve tumor oxygenation are still not fully understood.
Initially, it was hypothesized that selective killing of the endothelial cells would reduce their oxygen consumption and increase vascular permeability.
However, current findings also show that the combination has variable efficacy and is associated with increased toxicity.
This indicates that combining radiotherapy with angiostatic drugs not only holds opportunities but also provides several challenges.
Regarding the latter, promising preclinical observations instigated numerous clinical trials exploring the benefit of combining angiostatic drugs with radiotherapy.Hence, adequate scheduling is important to ensure that radiation is applied during the normalization window .In addition, to what extent vascular normalization occurs in the clinical setting and whether or not it contributes to better tumor oxygenation is still under debate [46, 47].This has instigated numerous efforts to optimize and clinically implement the combination of angiostatic drugs with radiation treatment.The results from past and present clinical trials that explored this combination therapy indeed show encouraging results.