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Receptor tyrosine kinase like orphan receptor 2 (ROR2) is a transmembrane protein that functions as a key receptor in the non-canonical Wnt signaling pathway, primarily by binding the ligand Wnt5a [1, 5]. It is essential for proper skeletal and neuronal development during embryogenesis, and its dysfunction is linked to genetic conditions such as Robinow syndrome and Brachydactyly type B [1, 2]. Although its expression is minimal in healthy adult tissues, ROR2 is frequently overexpressed in various cancers, including melanoma, osteosarcoma, and breast cancer, where it promotes epithelial-mesenchymal transition (EMT), cell migration, and metastasis [5]. This tumor-associated expression makes ROR2 a significant therapeutic target in oncology. Current clinical and preclinical strategies include antibody-drug conjugates (ADCs) like Ozuriftamab vedotin (BA3021) and NBE-002, which deliver cytotoxic payloads directly to ROR2-positive cells, as well as CAR-T cell therapies designed to harness the immune system against the receptor [3, 4]. Additionally, targeting ROR2 mRNA through RNA interference (siRNA) is being explored as a method to downregulate its expression and inhibit oncogenic signaling [5].
Targeted cell killing via antibody-drug conjugates, immune-mediated destruction via CAR-T cells, and inhibition of non-canonical Wnt signaling pathways.
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