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providing a mechanism by which hypoxia may promote treatment failure. These findings suggest that an inhibitor of HIF-1 activity may be useful as a therapeutic agent in combination with signal transduction inhibitors that target either the tumor cells or the endothelium. Angiogenesis inhibitors, such as antibodies against VEGF or smallmolecule inhibitors of VEGF receptors, may be particularly effective against tumor vessels that lack pericyte coverage .84 Based upon the results of expressing HIF-1αDN in gastric cancer cells, inhibition of HIF-1 activity may inhibit pericyte coverage and thus promote the effects of angiogenesis inhibitors. A recent microarray analysis of the transcriptional programs affected by treatment of endothelial cells with the anti-angiogenic agent endostatin revealed a significant reduction in the expression of HIF-1 target genes,85 a result that is consistent with the finding that HIF-1 controls both the production of angiogenic growth factors/cytokines and cell-autonomous responses of endothelial cells to angiogenic signals.7,74

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