Molecular Mechanisms of Resistance to Tumour Anti-Angiogenic Strategies

Figure 1

Molecular mechanisms involved in tumor anti-angiogenesis therapies resistance. (1) Following anti-VEGF therapies, redundant angiogenic factors are produced by tumour cells. Antiangiogenic treatments reduce and normalize tumour vasculature but increase intratumour hypoxia (2). Hypoxia induces SDF-1α which recruits BMDCs such as CD11b+Gr1+, redundant angiogenic factors (1), and activates HGF/c-MET pathway (5). BMDCs are activated by factors secreted by stroma cells (SDF-1∝, G-CSF, and IL-6). Inhibition of VEGF induces endothelial cells apoptosis and pericytes attachment to endothelial cells is loosed (5). New vessels could be recruited to tumour site by vessel cooption (6). Finally mechanisms involved in tumor anti-angiogenesis resistances lead to select more invasive and metastatic tumour cells (3).