At the Bench: Pre‐clinical evidence for multiple functions of CXCR4 in cancer. Issue 5 (26th October 2020)

• Record Type: Journal Article
• Authors: Luker, Gary D; Yang, Jinming; Richmond, Ann; Scala, Stefania; Festuccia, Claudio; Schottelius, Margret; Wester, Hans‐Jürgen; Zimmermann, Johann
• Is Part Of: Journal of leukocyte biology. Volume 109:Issue 5(2021)
• Page Start: 969
• Page End: 989
• Publication Date: 2020-10-26
• Subjects: chemokine -- CXCL12 -- CXCR4 antagonist -- CXCR4 inhibitor -- radioimaging -- tumor; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.2BT1018-715RR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: Signaling through chemokine receptor, C‐X‐C chemokine receptor type 4 (CXCR4) regulates essential processes in normal physiology, including embryogenesis, tissue repair, angiogenesis, and trafficking of immune cells. Tumors co‐opt many of these fundamental processes to directly stimulate proliferation, invasion, and metastasis of cancer cells. CXCR4 signaling contributes to critical functions of stromal cells in cancer, including angiogenesis and multiple cell types in the tumor immune environment. Studies in animal models of several different types of cancers consistently demonstrate essential functions of CXCR4 in tumor initiation, local invasion, and metastasis to lymph nodes and distant organs. Data from animal models support clinical observations showing that integrated effects of CXCR4 on cancer and stromal cells correlate with metastasis and overall poor prognosis in >20 different human malignancies. Small molecules, Abs, and peptidic agents have shown anticancer efficacy in animal models, sparking ongoing efforts at clinical translation for cancer therapy. Investigators also are developing companion CXCR4‐targeted imaging agents with potential to stratify patients for CXCR4‐targeted therapy and monitor treatment efficacy. Here, pre‐clinical studies demonstrating functions of CXCR4 in cancer are reviewed. Graphical Abstract: Review examines CXCR4‐dependent mechanisms in tumor environments of solid cancers, the current status of radioimaging for CXCR4, and the landscape of CXCR4 modulators.