A large body of clinical evidence exists to suggest that tumor hypoxia negatively impacts
radiotherapy. As a result, there has been longstanding active research into novel methods of improving
tumor oxygenation, targeting hypoxic
tumor cells, and otherwise modulating the effect
hypoxia has on how
tumors respond to radiation. Over time, as more has been learned about the many ways
hypoxia affects
tumors, our understanding of the mechanisms connecting
hypoxia to radiosensitivity has become increasingly broad and complicated. This has opened up new potential avenues for interrupting
hypoxia's negative effects on
tumor radiosensitivity. Here, we will review what is currently known about the spectrum of influence
hypoxia has over the way
tumors respond to radiation. Particular focus will be placed on recent discoveries suggesting that
hypoxia-inducible factor-1 (HIF-1), a
transcription factor that upregulates its target genes under hypoxic conditions, plays a major role in determining
tumor radiosensitivity. HIF-1 and/or its target genes may represent therapeutic targets which could be manipulated to influence
hypoxia's impact on
tumor radiosensitivity.