Therefore, the antiangiogenic effect of sorafenib results from blockade of the HIF-1α/VEGF pathway.123,124 Sorafenib suppresses the synthesis of hypoxia-inducible factor 1 (HIF-1α), resulting in a decrease in VEGF expression and tumor angiogenesis in HCC.125 In addition, acquired sorafenib resistance and an anoxic microenvironment show an interesting correlation. The gene discussed is HIF1A; the disease is hepatocellular carcinoma.