Colony-stimulating factor 1 receptor (CSF1R) (CSF1R)

The Colony-stimulating factor 1 receptor (CSF1R), also known as the Fms receptor tyrosine kinase, is a cell-surface protein that plays a critical role in the survival, proliferation, and differentiation of mononuclear phagocytes, including macrophages and osteoclasts (UniProt: P07333). It is activated by two primary ligands, Colony Stimulating Factor 1 (CSF1) and Interleukin-34 (IL-34), which trigger autophosphorylation of the receptor's intracellular tyrosine kinase domain (PubMed: 22490281). In the context of oncology, CSF1R is frequently overexpressed or activated in the tumor microenvironment, where it promotes the recruitment of tumor-associated macrophages (TAMs) that suppress anti-tumor immunity and facilitate angiogenesis (PubMed: 27069712). Beyond cancer, mutations in the CSF1R gene are linked to rare neurodegenerative disorders like Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), and its signaling is implicated in chronic inflammatory conditions (NCBI Gene: 1436). Therapeutic strategies targeting CSF1R include small molecule inhibitors and monoclonal antibodies, which aim to deplete immunosuppressive macrophages or inhibit pathological bone resorption (PubMed: 31394965). Clinical use of these agents, such as pexidartinib, requires careful monitoring for side effects like hepatotoxicity (FDA: Turalio Prescribing Information).

Other names

Macrophage colony-stimulating factor receptorM-CSFRCD115Fms proto-oncogeneC-FMSProto-oncogene c-Fms

Small molecule inhibition of the intracellular tyrosine kinase domain (ATP-competitive) or monoclonal antibody-mediated blockade of the extracellular ligand-binding domain to prevent receptor activation and downstream signaling (PubMed: 31394965).