ResearchVEGF
Genentech Biooncology

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What happens when VEGF inhibition is stopped?

Rapid vessel regrowth following withdrawal of an anti-VEGF agent15

Rapid vessel regrowth following withdrawal of an anti-VEGF agent
CD31 staining shows significant vascular regression from baseline (A) after 7 days of treatment with an anti-VEGF agent (B). After withdrawal of the agent, vessel regrowth is observed within 2 days (C, arrows) and vascularity returns to baseline levels after 7 days (D). Note: the anti-VEGF agent used in this model was AG-013736, a VEGF TKI with a terminal half-life of 2 to 5 hours.23

While continued VEGF inhibition is thought to maintain important anti-angiogenic effects that keep tumor cells from growing and spreading, cessation of VEGF suppression may diminish those effects. In fact, in preclinical models, withdrawal of an anti-VEGF agent has been shown to result in rapid regrowth of tumor vasculature.15-18 This vessel regrowth may be particularly rapid along the basement membrane tracks left by previously regressed vasculature.17,18 These proposed effects influence clinical trial design. Specifically, many clinical trials with anti-VEGF agents have been designed to maintain VEGF inhibition, even in instances in which administration of accompanying antitumor compounds may be modified.19-22

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Understanding tumor progression

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