In a hypoxic microenvironment, HIFs can induce the synthesis of various GFs, including epidermal growth factor (EGF), transforming growth factor-α (TGF- α), insulin-like growth factors 1 and 2 (IGF1 and IGF2), platelet-derived growth factor (PDGF), endothelin1 (EDN1), adrenomedullin (ADM) and erythropoietin (EPO) in renal cell carcinoma, colorectal carcinoma, pancreatic cancer, breast cancer, prostate cancer, melanoma, and ovarian cancer cells [60,61]. The gene discussed is ADM; the disease is melanoma.