CXCR4-targeted theranostics in acute leukemia: disrupting leukemic cell-microenvironment interactions with pentixafor and pentixather

  • Med Oncol. 2025 Aug 4;42(9):402. doi: 10.1007/s12032-025-02924-w.
Sana Rahimian  #  1 ,  Hossein Najafi  #  2 ,  Mohammad Doroudian  #  3
Affiliations
  • 1. Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Islamic Republic of Iran.
  • 2. Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Islamic Republic of Iran.
  • 3. Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Islamic Republic of Iran. [email protected].
  • # Contributed equally.
PMID: 40754635 DOI: 10.1007/s12032-025-02924-w
Abstract

The CXCR4/CXCL12 signaling axis governs leukemic stem cell dynamics within the bone marrow niche, driving migration, survival, and therapy resistance. This review examines a CXCR4-directed theranostic strategy for acute leukemia using Pentixafor and Pentixather. Pentixafor enables non-invasive visualization of CXCR4 expression, while Pentixather delivers targeted radiotherapy to CXCR4-expressing leukemic cells. We analyze how disrupting CXCR4-mediated leukemic cell-niche interactions enhances treatment efficacy and improves clinical outcomes in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). By integrating imaging and therapy, this approach offers a novel strategy to overcome microenvironment-mediated chemoresistance in hematologic malignancies. It advances personalized medicine by stratifying patients for CXCR4-targeted therapy and preserves functional hematopoietic niches, ultimately improving patient care.

Keywords
Acute leukemia; Bone marrow niche; CXCR4; Pentixafor; Pentixather; Theranostics.
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