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 Printable version |
Hypoxia-inducible factor 1: regulation, involvement in carcinogenesis and target for anticancer therapy |
Bulletin du Cancer. Volume 92, Number 2, 119-27, Février 2005, Synthèse
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 Résumé
Article gratuit
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Author(s) : Éric Clottes |
Summary : Hypoxia-inducible factor-1 is a heterodimer made up of an oxygen-regulated HIF1α subunit and a constitutively expressed HIF1β subunit. Among the 70 target genes of HIF-1 known so far, several are involved in angiogenesis, erythropoiesis, cell proliferation, cell viability, and glucose and iron metabolisms. Intratumoral hypoxia or genetic alterations can lead to HIF-1 α over-expression. HIF-1 over-expression has been associated with an increased patient mortality rate in many cancer types. Also, in vitro suppression of hif1α gene expression has been shown to be efficient in tumour growth repression. During the past five years, drugs able to indirectly inhibit HIF1 activity have been rationally or empirically developed. Some are currently evaluated in clinical trials, but further work has still to be undertaken to rationally identify new specific inhibitors of HIF1 and to test their efficacy as anticancer therapeutics. This review focuses on HIF1 regulation, HIF1 involvement in tumour promotion, the different HIF-1 inhibitors currently tested and their mechanisms of action. |
Keywords : hypoxia, prolyl hydroxylase, acetyltransferase, tumour, therapy |
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