[Hypoxia and angiogenesis]

The presence of hypoxic regions within solid tumours is associated with a more malignant tumour phenotype and worse prognosis. To obtain a blood supply and protect against cellular damage and death, oxygen-deprived cells in tumours alter gene expression, resulting in resistance to therapy. Hypoxia is sensed at the cellular level, leading to the activation of molecular pathways to cope with this stress. The key mediator of hypoxia response is HIF1alpha, a member of the hypoxia-inducible factor (HIF) family of proteins. This protein is a transcription factor that stimulates the expression of a multitude of genes important for adaptation to hypoxia, including those encoding angiogenesis. Angiogenesis is stimulated by vascular endothelial growth factor (VEGF), a HIF target gene, to increase blood flow towards oxygen-deprived tissues. This regulation of angiogenesis by hypoxia and HIF is crucial during embryonic development, but also for recovery after ischemic injury. Angiogenesis is one of the physiological responses to hypoxia. Nevertheless, angiogenesis has also deleterious effects by favouring tumour growth.