The role of CXCR4 in multiple myeloma: Cells’ journey from bone marrow to beyond

CXCR4 is a pleiotropic chemokine receptor which acts through its ligand CXCL12 to regulate diverse physiological processes. CXCR4/CXCL12 axis plays a pivotal role in proliferation, invasion, dissemination and drug resistance in multiple myeloma (MM). Apart from its role in homing, CXCR4 also affects MM cell mobilization and egression out of the bone marrow (BM) which is correlated with distant organ metastasis. Aberrant CXCR4 expression pattern is associated with osteoclastogenesis and tumor growth in MM through its cross talk with various important cell signalling pathways. A deeper insight into understanding of CXCR4 mediated signalling pathways and its role in MM is essential to identify potential therapeutic interventions. The current therapeutic focus is on disrupting the interaction of MM cells with its protective tumor microenvironment where CXCR4 axis plays an essential role. There are still multiple challenges that need to be overcome to target CXCR4 axis more efficiently and to identify novel combination therapies with existing strategies. This review highlights the role of CXCR4 along with its significant interacting partners as a mediator of MM pathogenesis and summarizes the targeted therapies carried out so far.