Macrophage colony-stimulating factor 1 receptor (CSF1R) (CSF1R)

Macrophage colony-stimulating factor 1 receptor (CSF1R), also known as CD115 or c-Fms, is a cell-surface receptor tyrosine kinase that is essential for the survival, proliferation, and differentiation of mononuclear phagocytes, including macrophages, monocytes, and osteoclasts [1, 2]. Upon binding its ligands, CSF1 or IL-34, the receptor undergoes dimerization and autophosphorylation, triggering downstream signaling pathways such as MAPK, PI3K/AKT, and PLCγ [3, 4]. These pathways regulate the recruitment and function of myeloid cells throughout the body. In the tumor microenvironment, CSF1R signaling is frequently exploited to recruit tumor-associated macrophages (TAMs), which contribute to immunosuppression, angiogenesis, and tumor progression [5]. Consequently, CSF1R is a major therapeutic target in oncology, particularly for tenosynovial giant cell tumors (TGCT) and as a strategy to reprogram the immune microenvironment in solid tumors [6]. Drugs targeting this receptor include small molecule kinase inhibitors like pexidartinib and various monoclonal antibodies designed to block ligand binding or receptor activation [7, 8]. Beyond cancer, CSF1R is also implicated in neurodegenerative diseases and inflammatory conditions where microglial or macrophage activity is dysregulated [9]. Sources: [1] UniProt P07333; [2] NCBI Gene ID 1436; [3] PMID: 27141351; [4] StatPearls, CSF1R Signaling; [5] PMID: 31434513; [6] FDA Turalio Label; [7] PMID: 24441665; [8] PMID: 30217935; [9] PMID: 28213343.

Other names

CSF-1RM-CSF receptorCD115c-FmsProto-oncogene c-FmsFMS

Inhibition of the intracellular tyrosine kinase domain by competing with ATP binding, or blockade of the extracellular ligand-binding domain using monoclonal antibodies to prevent receptor dimerization and activation.