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In preclinical models a number of tumors do not respond at all, or respond initially but become resistant at a late stage of VEGF inhibition . In some experimental cases, such therapy may even increase tumor invasiveness and metastasis . A further problem is that although this therapy is highly specific, patients are not selected on the basis of pathways of sensitivity or resistance in their tumors. Thus, tumor resistance to VEGF inhibition has become a major obstacle to the effectiveness of antiangiogenic agents in the clinic. Clearly, understanding the resistance mechanisms will enhance anti-VEGF efficacy by developing new therapeutic approaches or rational drug combinations |
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