Current Medicinal Chemistry
Current Medicinal Chemistry
5 years ago

Targeting CXCL12/CXCR4 Axis in Tumor Immunotherapy.

Wang G, Burow M, Liu M, Guo S, Zhou W
Chemokines, which have chemotactic abilities, are comprised of over 50 family members. Through binding to the 7-transmembrane domain of G-protein-coupled receptors (GPCR), they function in immune cells by trafficking and regulating cell prolif¬eration, differentiation, activation, and migration, homing under both physiologic and pathologic conditions. The alpha-chemokine receptor CXCR4 for the alpha-chemokine stromal cell-derived-factor-1 (SDF-1) is most widely expressed by tumors. CXCL12/CXCR4 axis is a major culprit for human tumor because of its crucial role in tumor initiation and progression by activating a number of signaling pathways, such as ERK1/2, ras, PLC/ MAPK, p38 MAPK, and SAPK/ JNK, as well as regulating cancer stem cells. CXCL12/CXCR4 antagonists have been developed, which have shown promising results in both in vitro and in vivo anti-cancer activity in several tumor types. This review provides an evaluation of CXCL12/CXCR4 as a potential therapeutic target for human tumors; it also focuses on the synergistic effects of inhibition of CXCL12/CXCR4 axis and immunotherapy as well as chemotherapy. Together, CXCL12/CXCR4 axis can be a potential therapeutic target for tumors and used with immunotherapy for additive effects.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28875842

DOI: PubMed:28875842

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