The CXCL12/CXCR4/ACKR3 Axis in the Tumor Microenvironment: Signaling, Crosstalk, and Therapeutic Targeting

Elevated expression of the chemokine receptors CXCR4 and ACKR3 their cognate ligand CXCL12 is detected in a wide range tumors tumor microenvironment (TME). Yet, molecular mechanisms by which CXCL12/CXCR4/ACKR3 axis contributes to pathogenesis are complex not fully understood. To dissect role this cancer, we discuss its ability impinge on canonical less conventional signaling networks different cancer cell types; bidirectional crosstalk, notably with receptor tyrosine kinase (RTK) other factors present TME; infiltration immune cells that supporttumor progression. We current emerging avenues target axis. Coordinately targeting both RTKs CXCR4/ACKR3 and/or an attractive approach consider multitargeted therapies. In addition, inhibiting infiltrating or reactivating system along modulating TME has therapeutic promise.