HIF-1 signaling: A key orchestrator of cancer radioresistance

Hypoxia is a big roadblock for cancer radiotherapy, in which the hypoxia-inducible factor (HIF-1) creates a microenvironment and cancer cells’ intrinsic signaling networks conferring radioresistance to cancers. HIF-1 is a heterodimeric transcription factor HIF-1α/HIF-1β, that regulates the transcription of a broad range of down-stream genes possessing an E-box-like hypoxia response element (HRE). The expression of HIF-1α is oxygen-sensitive while HIF-1β is constitutively expressed. In addition to hypoxia, ionizing radiation can also induce the expression of HIF-1α. The HIF-1 modulates a set of signaling pathways to cause profound effects on the response of cancer to radiotherapy, including radiation-induced DNA damage response (DDR), vasculogenesis and glucose metabolism reprograming, epithelial mesenchymal transition (EMT), etc. In this review, our aim is to summarize the current knowledge about the role and the related signal pathways of HIF-1 in association with the resistance of cancers to radiotherapy. Targeting HIF-1 and its signal pathways is a promising strategy for sensitization of cancers to radiotherapy.