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The current understanding of tumor biology, based primarily on preclinical observations, suggests that antitumor strategies must be made versatile over time in order to remain effective.17 In particular, while multiple angiogenic factors may be activated over the course of a tumor life cycle, VEGF is the only one known to be critical throughout.19 Therefore, the strategy of maintaining direct inhibition of the VEGF ligand—supplemented by selective targeting of secondary pathways as they emerge—continues to be explored in both the laboratory and the clinic.20,21
As observed in preclinical models, the ability to maintain direct VEGF inhibition as part of an overall antitumor strategy may be a function of the specificity of direct VEGF inhibitors. This specificity may facilitate combination with approaches that target other mechanisms of tumor proliferation.4,6
Indeed, the anti-angiogenic effects of direct VEGF inhibition have been observed in a wide range of preclinical settings. In addition to antitumor activity demonstrated in single-agent experiments, direct VEGF inhibition has been shown to be active in combination with a range of modalities that target other mechanisms of tumor proliferation.18 This ability to apply direct and continuous VEGF inhibition, either alone or with other modalities, may add versatility to an overall antitumor approach.17 Further preclinical investigation is warranted to evaluate the versatility of direct VEGF inhibition.
