EPAS1 and neoplasm: These include agents which interfere with the unfolded protein response (UPR), a mechanism that contributes to tumor cell survival under hypoxia, or substances which block HIF-1α and HIF-2α (hypoxia-induced factors 1α and 2α)-linked signaling pathways that adapt tumor cells to hypoxia, e.g., by inducing metabolic reprogramming, enhancing tumor cell survival, and supporting angiogenesis and metastasis [4,69].