VEGF Blockade

Inhibition of VEGF has recently been shown to be effective in clinical trials of some human cancers (Glade-Bender et al. 2003). VEGF blockade has also shown efficacy in preclinical models of human neu-roblastoma, using agents that target the ligand or its VEGFR2 receptor (Davidoff et al. 2001b; Klement et al. 2000; Rowe et al. 2000). More recent reports demonstrate that neuroblastoma tumors may co-opt host vasculature early in development (Kim et al. 2002a).Partial blockade of VEGF may prolong co-option, which presumably contributes to tumor perfusion and supports continued, although reduced, tumor growth. Use of very high-affinity VEGF-bind-ing molecules, such as the recently described novel fusion construct VEGF-Trap, can cause regression of such co-opted vessels (Holash et al. 2002; Kim et al. 2002a); thus, selection of optimal VEGF blocking strategies for testing in patients with neuroblastoma may require selection of agents based on specific biochemical and pharmacologic properties.

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