MERTK (MER Proto-Oncogene, Tyrosine Kinase) is a receptor tyrosine kinase belonging to the TAM family (TYRO3. AXL, MERTK), which regulates critical cellular processes such as proliferation, survival, migration, and immune modulation. It is activated by binding to ligands like Gas6 and Protein S, initiating downstream signaling pathways. MERTK is widely expressed in epithelial, immune, and neural cells, playing roles in tissue homeostasis, phagocytosis, and resolution of inflammation. Dysregulation of MERTK is implicated in pathologies, including cancer, autoimmune diseases, and retinal disorders.
In cancer, MERTK overexpression promotes tumor survival, immune evasion, and therapy resistance by suppressing anti-tumor immunity. This has spurred interest in developing MERTK-targeted therapies, such as monoclonal antibodies. MERTK antibodies block ligand binding or receptor activation, inhibiting oncogenic signaling and enhancing immune recognition. Preclinical studies show efficacy in solid tumors (e.g., melanoma, lung cancer) and hematologic malignancies.
MERTK antibodies also hold promise in treating age-related macular degeneration (AMD) by modulating retinal pigment epithelium phagocytosis. Additionally, they are explored in autoimmune contexts to counteract excessive TAM-mediated immunosuppression. Challenges include optimizing selectivity to avoid off-target effects and overcoming resistance mechanisms. Several MERTK-targeting antibodies are in early-stage clinical trials, highlighting their therapeutic potential across diverse diseases.