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The Erythropoietin-producing hepatocellular (Eph) receptor family constitutes the largest subfamily of receptor tyrosine kinases (RTKs) in the human genome (UniProt, 2023). These receptors are divided into two classes, EphA and EphB, based on their sequence homology and binding affinity for their membrane-bound ligands, known as ephrins (NCBI, 2022). Eph receptors play a critical role in mediating cell-to-cell communication, influencing processes such as axon guidance, angiogenesis, and tissue patterning during development (PubMed, PMID: 25145844). In adult tissues, dysregulation of Eph signaling is frequently associated with various pathologies, most notably cancer, where they contribute to tumor growth, metastasis, and neoangiogenesis (Nature Reviews Cancer, 2014). Because of their cell-surface expression and involvement in disease progression, Eph receptors are significant targets for therapeutic intervention, including small-molecule kinase inhibitors like dasatinib, monoclonal antibodies like KB004, and antibody-drug conjugates (PubChem, 2024). Their unique bidirectional signaling mechanism, where both the receptor and the ligand can initiate intracellular signals, adds a layer of complexity to their role in physiology and disease (PubMed, PMID: 24457415).
Inhibition of receptor tyrosine kinase activity, disruption of ephrin ligand-mediated bidirectional signaling, and antibody-mediated targeting of receptor-expressing cells (PubMed, PMID: 25145844).
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