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 downstream genes possessing an E-box-like hypoxia response element(HRE).The expression of HIF-1αis oxygensensitive while HIF-1βis 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.