ScienceVEGF

Strategies for inhibiting the VEGF pathway

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While VEGF is the predominant mediator of angiogenesis, there are different strategies for inhibiting its pathway. The two primary strategies include inhibiting either the VEGF ligand (e.g. ligand antibodies or soluble receptors) or the VEGF receptor (e.g. TKIs or receptor antibodies).¹ Anti-VEGF strategies that specifically target the ligand, such as VEGF antibodies, specifically inhibit pathways mediated by VEGF and therefore may inhibit angiogenesis without disrupting other ‘off target’ pathways.^2–4 Anti-VEGF strategies that target the receptor, such as TKIs, have a wider range of inhibitory effects and may disrupt other secondary pathways that are also mediated through receptor kinases – a factor associated with unwanted non-VEGF mediated side effects.^2,3,5–7

 

In addition, directly targeting VEGF has been shown to result in important antivascular effects that may be sustainable. In both preclinical and clinical models, an anti-VEGF antibody significantly reduced microvascular density, intratumoural pressure and neovascularisation.^8–11 These effects have been observed to occur rapidly (in some cases, after a single infusion). It is also important to note that the relatively long half-life of monoclonal antibodies allows for a maintained anti-VEGF effect.^2,8