Ephrin receptors (EphRs) are receptor tyrosine kinases. The main function of the EphRs is mediation of contact-dependent cell-cell communication, via interaction with membrane-bound ephrin ligands. EphR-ephrin complexes generate bidirectional signals with effects on both the receptor- and ligand-expressing cells. "Forward" signaling involves prototypical activation of the receptors' RTK domain upon ligand interaction, but also by receptor-receptor cis interactions (or receptor clustering) [2,9]. EphRs regulate effector proteins including Rho and Ras GTPases and Akt/mTORC1. "Reverse" signalling occurs in the ephrin-expressing cells, a function that appears to be mediated by ephrin-B phosphorylation by Src family kinases. The ephrin signalling pathway is active in many developmental processes and in adult tissue homeostasis [1,3-5,7]. Aberrant ephrin pathway function has been implicated in cancer, and in particular its role in tumour neoangiogensis [8], highlights elements of this pathway as oncology drug targets [1,6].

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