At present, a number of evidences, as for the paradoxical switch in biologic effects (from promoting to suppressing) in certain cancers [14], as well as Eph/Ephrins ecto-domain shedding which causes post-translational truncation of the receptor kinases [15] all point at the possibility that EphB4 reverse cellular effects in the cells where it is expressed may be the result of both EphrinB2 ligand-dependent and ligand-independent signals. This evidence concerns the gene EPHB4 and cancer.