Clinical evidence of occurrence of VM in patients is strongly correlated with high risk of metastasis, poor prognosis, cancer recurrence and worse survival for patients of variety of cancers.81 Previous report entails the resistance of VM to anti-angiogenic inhibitors such as endostatin and TPN-470 in B16F10 murine melanoma model, as well as in melanoma tumor cells.83 It is interesting to note that hypoxia induces VM and, of note, CSCs, which possess tumor recurrence abilities, have a crucial role in VM.84 This evidence concerns the gene COL18A1 and melanoma.