Targeting CSF1R: The development of small molecule inhibitors for cancer and other diseases

Area of Science:

• Biochemistry
• Molecular Biology
• Immunology

Background:

• Colony-stimulating factor 1 receptor (CSF1R) is a class III receptor tyrosine kinase crucial for macrophage function.
• CSF1R signaling is implicated in cancer, inflammation, neurodegeneration, and skeletal disorders.
• Dysregulation of CSF1R contributes to tumor progression and immune evasion via tumor-associated macrophages (TAMs).

Purpose of the Study:

• To review the structure, biological functions, and signaling pathways of CSF1R.
• To elucidate the pivotal role of CSF1R in various disease pathologies.
• To provide an overview of small-molecule CSF1R inhibitors in clinical and preclinical development.

Main Methods:

• Literature review of CSF1R structure, function, and signaling.
• Analysis of CSF1R's role in disease pathogenesis.
• Medicinal chemistry perspective on small-molecule CSF1R inhibitors.

Main Results:

• CSF1R is central to macrophage regulation and influences the tumor microenvironment (TME).
• Targeting CSF1R offers a promising therapeutic avenue for multiple diseases.
• Advances in small-molecule CSF1R inhibitors are detailed, covering both clinical and preclinical stages.

Conclusions:

• CSF1R inhibitors represent a significant therapeutic strategy for diseases involving CSF1R dysregulation.
• Further research into CSF1R inhibitors is warranted, addressing future perspectives and challenges.
• Understanding CSF1R's multifaceted roles provides insights for drug development.