For example, treatment of breast cancer with sunitinib and bevacizumab increased the CSC population through HIF-1 activation of Wnt pathway [242], and in pancreatic cancer and glioblastoma the use of a VEGFR and TKR inhibitor also increased the risk of invasion and metastasis related to intratumor hypoxic states [243–245]. This evidence concerns the gene TKTL1 and familial pancreatic carcinoma.