Increased expression or activation of EPHs can induce downstream signaling cascades, such as those mediated by AKT, ERK, MAPK, mTOR, Rac1, and Cdc42 [67,70,71,74,91,113] in CNS tumors, PKCγ, ERK1-2, and CDK4, with c-RAF and VEGF as target genes in neuroendocrine tumors [76,77], and Akt and MAPK in sarcomas [104,105,106], that overall enhance tumor cell proliferation and invasive properties. This evidence concerns the gene CDK4 and neuroendocrine neoplasm.