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Chemokines can induce chemotactic cell migration by interacting with G protein-coupled receptors to play a significant regulatory role in the development of cancer. CXC chemokine-12 (CXCL12) can specifically bind to CXC chemokine receptor 4 (CXCR4) and is closely associated with the progression of cancer via multiple signaling pathways. Over recent years, many CXCR4 antagonists have been tested in clinical trials; however, Plerixafor (AMD3100) is the only drug that has been approved for marketing thus far. In this review, we first summarize the mechanisms that mediate the physiological effects of the CXCL12/CXCR4 axis. Then, we describe the use of CXCL12/CXCR4 antagonists. Finally, we discuss the use of nano-based drug delivery systems that exert action on the CXCL12/CXCR4 biological axis.
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http://dx.doi.org/10.3390/pharmaceutics14081541 | DOI Listing |
Cell Chem Biol
August 2025
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Media Lab, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address:
The CXCR4/CXCL12 axis is vital for tumor metastasis and immune evasion in various cancers. However, developing effective inhibitors is challenging due to complex intracellular interactions and limitations of soluble receptor drugs targeting single transmembrane proteins. Here, we engineered a water-soluble CXCR4-Fc molecular trap by fusing a redesigned CXCR4 variant with the IgG1-Fc domain.
View Article and Find Full Text PDFFront Oncol
July 2025
Department of Orthopedics, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Osteosarcoma (OS) is the most common primary malignant bone tumour of childhood, yet five-year survival has plateaued at ~60-70% for localised disease and plunges below 30% once metastasis emerges. Formerly viewed as a cell-intrinsic neoplasm entombed in mineralised bone, OS is now understood as a spatially stratified ecosystem whose immune-evasion niches choreograph progression. Three-dimensional spatial transcriptomics (3-D ST) fuses barcode-based transcript capture with volumetric reconstruction, preserving x-, y- and z-axis context and exposing concentric C1QC necrotic belts, MCAM (melanoma cell-adhesion molecule, CD146) peri-vascular corridors, hypoxic glycolytic rims and therapy-induced tertiary-lymphoid islets that collectively sequester cytotoxic lymphocytes.
View Article and Find Full Text PDFAdv Sci (Weinh)
August 2025
Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, P. R. China.
Gastric carcinoma (GC) remains a major global health challenge, requiring novel therapeutic approaches. This study investigates the efficacy of self-assembled M2pep-Cs NPs/Plerixafor nanoparticles in suppressing GC by targeting the CXCL12-CXCR4 signaling pathway and reprogramming tumor-associated macrophages (TAMs) to enhance anti-tumor immunity. The nanoparticles' physicochemical properties and biocompatibility are assessed using transmission electron microscopy, dynamic light scattering, and biological assays.
View Article and Find Full Text PDFSci Rep
May 2025
Laboratory of Research and Diagnosis of Gynecological Diseases of Xiamen City, Clinical Medical Research Center for Obstetrics and Gynecology Diseases of Fujian Province, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen Universit
Endometrial cancer (EC) is one of the most common malignancies in women. In recent years, immunotherapy has gradually become a significant treatment option. However, the mechanisms underlying immune checkpoint inhibitor (ICI)-related Adverse Events (AEs) remain poorly understood, posing significant challenges for optimizing clinical treatment strategies.
View Article and Find Full Text PDFJ Neurosci
June 2025
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102
The chemokine CXCL12 is a highly conserved peptide that regulates homeostatic processes in the brain throughout life. Recent work shows that CXCL12 increases dendritic spine density in cortical neurons, which requires activation of CXCL12's receptor CXCR4. This same pathway reverses cortical dendritic spine deficits and cognitive impairment in an animal model of neuroHIV.
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