At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer

Gary D. Luker, Jinming Yang, Ann Richmond, Stefania Scala, Claudio Festuccia, Margret Schottelius, Hans Jürgen Wester, Johann Zimmermann

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)969-989
Number of pages21
JournalJournal of Leukocyte Biology
Volume109
Issue number5
DOIs
Publication statusPublished - May 2021

Keywords

  • chemokine
  • CXCL12
  • CXCR4 antagonist
  • CXCR4 inhibitor
  • radioimaging
  • tumor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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