In addition, multiple studies have demonstrated that under hypoxia, cancer cells engage metabolic adaptation strategies to survive and grow by activating a relevant gene expression program through HIF-1α [33,34] whereby the oxygen-sensitive hypoxia inducible factor (HIF) transcriptional regulators HIF-1α and HIF-2α are overexpressed in many human NSCLC [18]. Here, EPAS1 is linked to cancer.