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

Journal of Bone Oncology
Tomalika Rahmat Ullah

Abstract

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.

Citations

Apr 9, 2020·Vaccines·Stefania ScalaElena Monica Borroni
Jun 3, 2020·Cancers·Anne-Victoire Michaud-RobertCaroline Bodet-Milin
Jul 15, 2020·Journal of Hematology & Oncology·Shunling YuanJi Zhang
Jan 8, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christos SachpekidisAntonia Dimitrakopoulou-Strauss
Jan 6, 2021·International Journal of Molecular Sciences·Fumiko Sekiguchi, Atsufumi Kawabata
Sep 9, 2020·Current Opinion in Pharmacology·Wei-Chih ChenLori A Hazlehurst
Oct 31, 2020·Cancers·Panagiotis NtellasGeorge Pentheroudakis
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Zucheng LuoJixin Xue
Apr 20, 2021·Frontiers in Oncology·Domenica GiannandreaRaffaella Chiaramonte
Jun 15, 2021·Frontiers in Immunology·Huating ChenBinghui Li
Aug 14, 2021·Frontiers in Cell and Developmental Biology·Sheng WangXiongwen Lv
Aug 28, 2021·International Journal of Molecular Sciences·Giuseppe MurdacaSebastiano Gangemi

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Methods Mentioned

BETA
GTPase
ubiquitination
xenograft

Clinical Trials Mentioned

NCT00322842
NCT00322387
NCT01359657
NCT02104427
NCT01105403
NCT01010880
NCT00743288
NCT00532675
NCT01023308

Software Mentioned

PANORAMA

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