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Roundabout homolog 1 (ROBO1) is a transmembrane receptor belonging to the immunoglobulin superfamily that plays a critical role in the Slit-Robo signaling pathway. Primarily known for its function in axon guidance and neuronal migration during development, ROBO1 acts as a receptor for Slit ligands to mediate repulsive signals (UniProt Q14126). In the context of oncology, ROBO1 is frequently overexpressed in various solid tumors, including lung, breast, and hepatocellular carcinomas, where it promotes cell proliferation, migration, and angiogenesis (PubMed: 26459322). The extracellular domain of ROBO1, which contains five immunoglobulin-like domains and three fibronectin type III repeats, is the primary site for ligand binding and a key target for therapeutic intervention. Monoclonal antibodies and radioimmunoconjugates targeting this domain are being explored to inhibit tumor metastasis or deliver cytotoxic radiation directly to cancer cells (PubMed: 23873657). However, therapeutic targeting must account for its physiological roles in the central nervous system and potential off-target effects on normal tissue development and maintenance (PubMed: 30104715).
Inhibition of Slit-Robo signaling by blocking ligand binding to the extracellular domain or targeted delivery of radionuclides for cell killing.
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