Figure 3: Tumors inevitably outgrow their blood supply, resulting in HIF- 1 activation as a result of the hypoxic microenvironment. HIF-1 regulates glycolysis, and because it is not expressed at elevated levels in normal tissues, makes for a good candidate for targeting tumor metabolism. HIF-1 regulates glycolysis, the principle source of carbon for tumor acidosis. Therefore HIF-1 targeting therapy efficacy can be measured by assessing changes in tumor extracellular pH.