In relation to targeting hypoxia-induced proteins, the protein kinase AKT has been shown to be activated under severe hypoxia (0.1% oxygen for 6-72 h) in both HPV-positive and HPV-negative HNSCC cell lines, and that the AKT inhibitor MK2206 alone significantly reduced HPV-positive and HPV-negative HNSCC cell line growth (sensitiser enhancement ratios of ~1.5)[50]. This evidence concerns the gene AKT1 and head and neck squamous cell carcinoma.