C-X-C chemokine receptor type 4 (CXCR4) and C-X-C motif chemokine ligand 12 (CXCL12) axis (CXCR4-CXCL12 axis)

The CXCR4-CXCL12 axis is a critical signaling pathway involving the G protein-coupled receptor C-X-C chemokine receptor type 4 (CXCR4) and its primary ligand, C-X-C motif chemokine ligand 12 (CXCL12), also known as stromal cell-derived factor 1 (SDF-1) (UniProt P61073, P48061). This axis plays a fundamental role in the regulation of hematopoietic stem cell homing to the bone marrow, leukocyte trafficking, and embryonic development, particularly in the cardiovascular and nervous systems (PMID: 15078139, 29022185). In oncology, the overactivation or overexpression of CXCR4 is associated with tumor growth, angiogenesis, and the directed metastasis of cancer cells to organs with high CXCL12 expression, such as the bone marrow, lungs, and liver (PMID: 20102927, 29022185). Additionally, CXCR4 serves as a major co-receptor for the entry of T-tropic HIV-1 into host cells (PMID: 15078139). Therapeutic strategies targeting this axis primarily involve CXCR4 antagonists, such as Plerixafor and Motixafortide, which are used to mobilize stem cells for transplantation and are being investigated for their potential to disrupt the protective tumor microenvironment and enhance the efficacy of chemotherapy and immunotherapy (FDA, PMID: 20102927). Emerging therapies like Mavorixafor target the axis to treat WHIM syndrome, a rare genetic immunodeficiency caused by gain-of-function mutations in CXCR4 (FDA).

Other names

CXCR4-SDF-1 axisSDF-1/CXCR4 axisCXCL12/CXCR4 axisStromal cell-derived factor 1/C-X-C chemokine receptor type 4 axisCD184FusinLESTRPBSF

Antagonism of the CXCR4 receptor to prevent binding of CXCL12, thereby inhibiting downstream signaling pathways such as PI3K/Akt and MAPK, and disrupting the homing of cells to specific niches.