EGF and neoplasm: EGF-bound p-EGFR upregulates at the nucleus the transcription of pro-survival/adaptation proteins, a key one being the hypoxia-inducing factor (HIF-1), which regulates hundreds of genes to allow adaptation to moderate to severe hypoxia (∼3–0.1% oxygen), which occurs at the later stages of tumour growth when partaking cells find themselves separated from the local vasculature (reviewed in [173]) (Figure 5F).