As soon as the tumor cannot be fueled by VEGF, an ability to circumvent this dependence is operative, feeding into a vicious cycle boosted by PGF, angiopoietins, and PDGF [65], activating several biological pathways such as VEGFR-2, mTOR, and heparin-binding EGF-like growth factor (HB-EGF)-epidermal growth factor receptor (EGFR) signaling [43,66,67,68] and acting as an intelligent evolving organism. This evidence concerns the gene HBEGF and neoplasm.