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  • Title: Targeting hypoxia and angiogenesis through HIF-1alpha inhibition.
    Author: Diaz-Gonzalez JA, Russell J, Rouzaut A, Gil-Bazo I, Montuenga L.
    Journal: Cancer Biol Ther; 2005 Oct; 4(10):1055-62. PubMed ID: 16294030.
    Abstract:
    Hypoxia 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.
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