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...