At the Bedside: Profiling and treating patients with CXCR4-expressing cancers

Miguel Martin, Ingrid A. Mayer, Annemiek M.E. Walenkamp, Constantin Lapa, Michael Andreeff, Alexandra Bobirca

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

The chemokine receptor, C-X-C chemokine receptor type 4 (CXCR4) and its ligand, C-X-C motif chemokine 12, are key mediators of hematopoietic cell trafficking. Their roles in the proliferation and metastasis of tumor cells, induction of angiogenesis, and invasive tumor growth have been recognized for over 2 decades. CXCR4 is a promising target for imaging and therapy of both hematologic and solid tumors. To date, Sanofi Genzyme's plerixafor is the only marketed CXCR4 inhibitor (i.e., Food and Drug Administration-approved in 2008 for stem cell mobilization). However, several new CXCR4 inhibitors are now being investigated as potential therapies for a variety of fluid and solid tumors. These small molecules, peptides, and Abs include balixafortide (POL6326, Polyphor), mavorixafor (X4P-001, X4 Pharmaceuticals), motixafortide (BL-8040, BioLineRx), LY2510924 (Eli Lilly), and ulocuplumab (Bristol-Myers Squibb). Early clinical evidence has been encouraging, for example, with motixafortide and balixafortide, and the CXCR4 inhibitors appear to be generally safe and well tolerated. Molecular imaging is increasingly being used for effective patient selection before, or early during CXCR4 inhibitor treatment. The use of radiolabeled theranostics that combine diagnostics and therapeutics is an additional intriguing approach. The current status and future directions for radioimaging and treating patients with CXCR4-expressing hematologic and solid malignancies are reviewed. See related review - At the Bench: Pre-Clinical Evidence for Multiple Functions of CXCR4 in Cancer. J. Leukoc. Biol. xx: xx–xx; 2020.

Original languageEnglish (US)
Pages (from-to)953-967
Number of pages15
JournalJournal of Leukocyte Biology
Volume109
Issue number5
DOIs
StatePublished - May 2021
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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