Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response

Hypoxia and free radicals, such as reactive oxygen and nitrogen species, alter the activity of the transcription factor HIF1, which can regulate tumour cell survival and angiogenesis. Intratumoural heterogeneity of these factors significantly affects HIF1 and consequently the response to cytotoxic therapy. 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.