EPAS1 and hepatocellular carcinoma: In addition, agents that inhibit reactive oxygen species generation, such as superoxide dismutase mimetics, have also been shown to decrease HIF levels.105 Inducing PHD enzyme activity with derivatives of α-ketoglutarate is also a method to target hypoxic areas of tumors, although it reduces signaling through both HIF-1α and -2α.46 Overexpression of the tumor suppressor protein pVHL inhibits HCC growth in mice by downregulating HIF-1α and HIF-2α.106