Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response.
Hypoxia and free radicals, such as reactive oxygen and nitrogen species, can alter the function and/or activity of the transcription factor hypoxia-inducible factor 1 (HIF1). Interplay between free radicals, hypoxia and HIF1 activity is complex and can influence the earliest stages of tumour development. The hypoxic environment of tumours is heterogeneous, both spatially and temporally, and can change in response to cytotoxic therapy. Free radicals created by hypoxia, hypoxia-reoxygenation cycling and immune cell infiltration after cytotoxic therapy strongly influence HIF1 activity. HIF1 can then promote endothelial and tumour cell survival. As discussed here, a constant theme emerges: inhibition of HIF1 activity will have therapeutic benefit.
Dewhirst
Mark W
MW
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cao
Yiting
Y
Moeller
Benjamin
B
D000818:Animals; D015687:Cell Hypoxia; D005609:Free Radicals; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000532:radiotherapy*; D009389:Neovascularization, Pathologic / Q000209:etiology*; D009569:Nitric Oxide / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D005609:Free Radicals; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D010100:Oxygen