Colony stimulating factor 1 receptor (CSF-1R) (CSF-1R)

The Colony stimulating factor 1 receptor (CSF-1R), also known as FMS, is a class III receptor tyrosine kinase primarily expressed on the surface of myeloid lineage cells, including monocytes, macrophages, microglia, and osteoclasts [1, 4]. Upon activation by its ligands, colony-stimulating factor 1 (CSF-1) and interleukin-34 (IL-34), the receptor undergoes dimerization and autophosphorylation, triggering downstream signaling pathways such as PI3K-AKT and MAPK that regulate cell survival, proliferation, and differentiation [4, 8]. In the context of oncology, CSF-1R signaling is a key driver in the recruitment and polarization of tumor-associated macrophages (TAMs), which foster an immunosuppressive microenvironment and promote tumor growth and metastasis [3, 14]. Beyond cancer, mutations in the CSF1R gene are linked to adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a progressive neurodegenerative disorder [2, 13]. Therapeutic targeting of CSF-1R involves small-molecule inhibitors like pexidartinib and monoclonal antibodies like emactuzumab, which aim to deplete TAMs or modulate microglial activity [7, 9]. Clinical use of these agents is often associated with safety concerns such as hepatotoxicity and periorbital edema [9]. The receptor also plays a critical role in bone metabolism by regulating osteoclastogenesis, making it a target for inflammatory bone diseases [1, 15]. Monitoring efficacy often involves measuring serum ligand levels or the expression of macrophage-specific biomarkers [13, 14].

Other names

FMSc-FMSCD115M-CSFRMacrophage colony-stimulating factor 1 receptorCSF-1 receptor

Tyrosine kinase inhibition and monoclonal antibody antagonism of ligand binding or receptor dimerization