pexidartinib and Colorectal-Neoplasms

Colony-stimulating factor 1 receptor (CSF1R), a classic tyrosine kinase receptor, has been identified as a proto-oncogene in multiple cancers. The CSF1/CSF1R axis is essential for the survival and differentiation of M2-phenotype tumor-associated macrophages (M2 TAMs). However, we found here that the CSF1R expression was abnormally down-regulated in colorectal cancer (CRC), and its biological functions and underlying mechanisms have become elusive in CRC progression.. The expression of class III receptor tyrosine kinases in CRC and normal intestinal mucosa was accessed using The Cancer Genome Atlas and Gene Expression Omnibus datasets and was further validated by our tested cohort. CSF1R was reconstructed in CRC cells to identify its biological functions. We found here that the CSF1R is silenced in CRC, and the reintroduced expression of the receptor in CRC cells can be cleaved by caspases and constrain tumor growth. Our findings revealed that CSF1R is a novel identified dependence receptor silenced in CRC. The silence abalienates its ligands to stimulate CSF1R expressed on M2 TAMs, which is an appealing therapeutic target for M2 TAM depletion and CRC treatment.

Topics: Animals; Colorectal Neoplasms; Ligands; Receptor Protein-Tyrosine Kinases; Tumor-Associated Macrophages

Inhibiting the polarization or survival of tumor-associated macrophages through blocking CSF-1/CSF-1R signal transduction has become a promising strategy for cancer immunotherapy. Herein, a series of (

Topics: Administration, Oral; Animals; Antineoplastic Agents; Cell Line, Tumor; Chemotaxis; Colorectal Neoplasms; Drug Discovery; Female; Humans; Immunotherapy; Macrophages; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Docking Simulation; Receptor, Macrophage Colony-Stimulating Factor; Structure-Activity Relationship; Urea