MST1R

MST1R (Macrophage stimulating 1 receptor), also known as RON (Recepteur d'Origine Nantais), is a receptor tyrosine kinase activated by its ligand macrophage-stimulating protein (MSP). Structurally related to the MET proto-oncogene, RON regulates cellular processes including proliferation, migration, and epithelial-mesenchymal transition through downstream signaling cascades such as PI3K/AKT, MAPK/ERK, and β-catenin pathways. Its aberrant activation, caused by overexpression, mutations, or alternative splicing, is implicated in tumor progression, metastasis, and therapeutic resistance across multiple cancers, particularly colorectal, breast, and pancreatic carcinomas. Emerging evidence also links dysregulated RON signaling to inflammatory disorders and organ fibrosis. Current therapeutic strategies target RON's kinase domain or ligand-binding sites, with clinical-stage candidates including small-molecule inhibitors (e.g., BMS-777607) and monoclonal antibodies demonstrating antitumor efficacy in Phase I/II trials. Recent preclinical advances explore bispecific antibodies and antibody-drug conjugates to overcome resistance mechanisms in RON-driven malignancies.