Hypoxia is widespread within most solid tumors. This stress situation is sufficient to activate the key transcription factor, hypoxia inducible factor (HIF)-1 that mediates the activation of the survival pathways in cancer cells. HIF-1 can also be induced by oxygen-independent genetic deregulations that activate a variety of oncogene signaling pathways or inactivate tumor suppressors. Increased tumor HIF-1 is often correlated with increased angiogenesis, malignant cancer progression, poor patient prognosis, and resistance to cancer therapies. HIF-1 is a proangiogenic transcription factor that interacts with a specific promoter sequence, called hypoxia response elements (HREs) in the regulatory region of the target DNA to stimulate transcription of multiple angiogenic factors including vascular endothelial growth factor (VEGF). In addition, HIF-1-targeted genes also include genes involved in cell proliferation, survival, invasion, and drug resistance. Due to...