Ephrin type-A receptor family (EphA)

The Ephrin type-A (EphA) receptor family is the largest subfamily of receptor tyrosine kinases (RTKs), comprising nine members (EphA1–EphA8 and EphA10) in humans (NIH, 2021). These receptors are characterized by their unique ability to engage in bidirectional signaling upon interaction with membrane-bound ephrin-A ligands, influencing both the receptor-expressing cell (forward signaling) and the ligand-expressing cell (reverse signaling) (Wikipedia, 2024). Biologically, EphA receptors are critical regulators of embryonic development, particularly in axon guidance, tissue boundary formation, and angiogenesis (NIH, 2005). In adult tissues, they maintain homeostasis but are frequently dysregulated in various pathologies, including cancer and neurodegeneration (Frontiers, 2020). In the context of disease, EphA receptors—most notably EphA2 and EphA3—are often overexpressed in solid tumors and hematological malignancies, where they promote cell proliferation, invasion, and metastasis (MDPI, 2021). However, their role is complex, as they can act as either tumor promoters or suppressors depending on the cellular environment and the presence of ligands (NIH, 2012). Therapeutic strategies targeting this family include small-molecule kinase inhibitors like dasatinib and bosutinib, monoclonal antibodies such as ifabotuzumab, and antibody-drug conjugates (ADCs) like MEDI-547 (MedChemExpress, 2024). While promising, targeting EphA receptors presents challenges such as achieving selectivity among family members and managing potential toxicities related to their roles in vascular and neurological health (PNAS, 2023).

Other names

EphA receptorsEphrin type-A receptorsEphA1-EphA8EphA10Erythropoietin-producing hepatocellular carcinoma type-A receptors

Inhibition of receptor tyrosine kinase activity, blockade of ephrin ligand binding, induction of receptor internalization and degradation, and antibody-drug conjugate-mediated cytotoxicity.