Vertical VEGF targeting: A combination of ligand blockade with receptor tyrosine kinase inhibition

The AZD2171-bevacizumab combination produced additive effects on tumour growth and reduced the number of proliferating cells relative to control. Bevacizumab did not influence tumour vascular necrosis whilst AZD2171 (p = 0.01) and the combination (p = 0.01) increased it. The number of mature tumour cells decreased significantly with the combination treatment only (p = 0.001), which induced the largest increase in the Bax/Bcl2 ratio (up to 25-fold) and a progressive 3-fold decrease in HIF1-α expression between 24 h and 192 h. The present data indicate that there is no redundancy in targeting the same angiogenic pathway with the presently tested clinically applicable drugs. The study provides a strong rationale for future clinical trials.