Since physiological hypoxia appears mainly in short hypoxia-re-oxygenation cycles and in fact cycling hypoxia significantly contributes to cancer-induced angiogenesis [21], one could hypothesize/conclude that metformin, by inhibiting HIF-1 signaling in short hypoxia intervals, may significantly inhibit MM-induced angiogenesis and in consequence progression of the disease. This evidence concerns the gene HIF1A and cancer.