Colony stimulating factor 1 receptor (CSF1R, c-Fms, CD115) is a tyrosine kinase transmembrane receptor for a cytokine called colony stimulating factor 1 (CSF-1). CSF-1R and its ligands, CSF-1 and interleukin 34 (IL-34), regulate the function and survival of tumor-associated macrophages, which are involved in tumorigenesis and in the suppression of antitumor immunity.
In solid tumors, targeting CSF-1R via either small molecules or antibodies has shown interesting results in vitro but limited antitumor activity in vivo. Blocking CSF-1/CSF-1R signaling represents a promising immunotherapy approach and several new potential combination therapies for future clinical testing.
PLX-3397 (pexidartinib) is an oral, potent, multi-target receptor tyrosine kinase inhibitor of CSF-1R, Kit, and Flt3 and is the most advanced selective CSF-1R inhibitor under clinical development. ABT-869 (linifanib) is an oral inhibitor of CSF-1R tyrosine kinase conducted a phase II trial in which ABT869 was administered to patients with hepatocellular carcinoma. BLZ-945 is another orally active, bioavailable, potent, and selective inhibitor of CSF-1R, which is currently being assessed in a first-in-man phase I/II study as a single agent or in combination with PDR-001 (anti-PD-1 antibody) in several advanced solid tumors. Besides, multiple anti-CSF-1R monoclonal antibodies have also entered clinical trials, including FPA-008 (cabiralizumab), RG-7155 (RO5509554), IMC-CS4 (LY3022855) and AMG-820.
The development of new CSF-1R/CSF-1 axis inhibitors represents an attractive method for managing patients with metastatic solid tumors refractory to the standards of care or with diffuse/relapsed TGCT. Recent clinical trials testing CSF-1R inhibitors as monotherapies have shown encouraging results in the management of PVNS but disappointing outcomes for the treatment of solid tumors.
1. Peyraud F, et al. Curr Oncol Rep. 2017 Sep 5;19(11):70.
2. Pyonteck SM, et al. Nat Med. 2013 Oct;19(10):1264-72.
3. Kogan M, et al. Anticancer Res. 2012 Mar;32(3):893-9.
4. Albert DH, et al. Mol Cancer Ther. 2006 Apr;5(4):995-1006.
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