Ephrin-A1 (EFNA1), a member of the ephrin family, functions as a ligand for Eph receptors, playing critical roles in angiogenesis, cell migration, and tissue development. Dysregulation of EFNA1 is implicated in cancer progression, metastasis, and pathological angiogenesis, making it a target for therapeutic intervention. EFNA1 interacts with Eph receptors (e.g., EphA2) to activate downstream signaling pathways like Rho GTPases and MAPK, influencing cell adhesion, proliferation, and survival. In tumors, EFNA1 is often overexpressed, promoting vascularization and invasiveness through crosstalk with VEGF and HIF-1α pathways.
EFNA1 antibodies are designed to block EFNA1-Eph receptor interactions, thereby inhibiting tumor growth and angiogenesis. Preclinical studies show that anti-EFNA1 antibodies reduce metastasis in breast, lung, and ovarian cancers by disrupting Eph-mediated signaling. Some antibodies also enhance immune responses by modulating the tumor microenvironment. Challenges include optimizing specificity to avoid off-target effects and overcoming resistance mechanisms. Clinical trials are exploring EFNA1-targeting agents, including monoclonal antibodies and bispecific constructs, often in combination with chemotherapy or immunotherapy. Research continues to elucidate EFNA1's dual roles in both pro- and anti-tumor contexts, aiming to refine therapeutic strategies.