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Oct 08, 2009
 |  BC Innovations  |  Targets & Mechanisms

Hitting HIF1 in cancer

Hypoxic regions in solid tumors can help trigger angiogenesis and invasion but are hard to attack with radiotherapy and chemotherapeutics because the oxygen-deprived areas are distant from any blood supply. Researchers at The Johns Hopkins University School of Medicine have now identified a compound, acriflavine, that directly inhibits a central player of the hypoxic response-hypoxia-inducible factor 1.1

Hypoxia-inducible factor 1 (HIF1) is a heterodimer consisting of the two proteins HIF1A (HIF1a) and HIF1B (HIF1b; see Figure 1, "Targeting HIF1 in cancer"). When oxygen is abundant, HIF1A is rapidly degraded by a family of three hypoxia-inducible factor prolyl hydroxylase (EGLN; HIF-PH; PHD) enzymes: PHD1, PHD2 and PHD3 (see Figure 1.I[a]). The enzymes increase HIF1A's affinity for a tumor-suppressor protein called von Hippel-Lindau (VHL) and target HIF1A to the proteasome for degradation (see Figure 1.I[b]).2,3

During oxygen deprivation, or hypoxia, HIF1A avoids proteasome-mediated degradation and instead accumulates...

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