EphB4 (Ephrin type-B receptor 4) is a member of the Eph family of receptor tyrosine kinases. Signaling pathways of these receptors play important roles in regulating numerous physiological processes during development including cell morphology, proliferation, migration and axonal guidance, dendritic spine formation and neural plasticity. Ephrins transduce bidirectional signals based on their distribution on the communicating cell surfaces. Eph receptors mediate forward signaling in one cell while ephrin ligands transmit reverse signaling in an adjacent cell^1,2.

Eph receptors consist of two large subfamilies: EphAs and EphBs that bind to either glycophosphatidylinositol (GPI)-anchored ephrin-A ligands or transmembrane ephrin-B ligands respectively. Each eph receptor may interact with multiple ligands, except for EPHB4, which only binds ephrin-B2².

EPHB4 is expressed primarily during embryonic development in neural tissue and immature vasculature. Studies show that EphB4 is implicated in the growth of several epithelial tumors and is a promising target in cancer therapy. EphB4 signaling was found to promote tumor growth, invasiveness, chemoresistance and tumor angiogenesis³_.