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lüll Targeting hypoxia and angiogenesis through HIF-1alpha inhibition Diaz-Gonzalez JA; Russell J; Rouzaut A; Gil-Bazo I; Montuenga LCancer Biol Ther 2005[Oct]; 4 (10): 1055-62Hypoxia is an important phenomenon in the tumor microenvironment. Hypoxic tumors are more aggressive and resistant to anti-neoplastic treatments. HIF-1alpha plays a major role in the response of tumors to hypoxia, and it is mainly responsible for the "angiogenic switch". HIF-1alpha contributes to tumor aggressiveness, invasiveness, and resistance to radiotherapy and chemotherapy. Targeting HIF-1alpha is an attractive strategy, with the potential for disrupting multiple pathways crucial for tumor growth. We review recent findings on the potential efficacy of small molecules to downregulate HIF-1alpha. These promising drugs inhibit HIF-1alpha synthesis or transcriptional activity by blocking a variety of steps in several different signaling pathways. Blocking HIF-1alpha activity should not only downregulate tumor angiogenesis, but also interfere with glycolytic metabolism and tumor cell growth. This strategy could also improve the efficiency of established tumor therapies.|*Gene Targeting[MESH]|Cell Hypoxia/*physiology[MESH]|Humans[MESH]|Hypoxia-Inducible Factor 1/*antagonists & inhibitors/genetics/metabolism[MESH]|Models, Biological[MESH]|Neovascularization, Pathologic/genetics/*metabolism/prevention & control[MESH] |