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Review Open Access

Potential of CXCR1/2 as a target for the treatment of inflammation and cancer (Review)

  • Authors:
    • Jing-Ming Zhong
    • Jing-Wei He
    • Ying Xiong
    • Meng-Ze Li
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Orthopedics, Luzhou Traditional Chinese Medicine Hospital, Luzhou, Sichuan 646000, P.R. China
    Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 227
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    Published online on: September 19, 2025
       https://doi.org/10.3892/etm.2025.12977
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Abstract

C‑X‑C motif chemokine receptor (CXCR)1 and CXCR2 are chemokine receptors that serve critical roles in mediating immune and inflammatory responses. Their activation by chemokines, such as C‑X‑C motif chemokine ligand (CXCL)8/IL‑8, can promote cell migration, proliferation and the release of additional inflammatory mediators, contributing to the progression of inflammatory diseases and cancers. By inhibiting the binding of CXCL8/IL‑8 to CXCR1 and CXCR2, SCH527123 aims to disrupt these harmful processes and offers a promising therapeutic strategy. Research on immunotherapy, particularly focusing on targeting specific immune receptors and pathways, is experiencing a surge of interest and progress. Exploration of SCH527123 as a novel CXCR1 and CXCR2 antagonist has highlighted the potential of this approach in treating various diseases, particularly those involving inflammation and cancers. The preclinical success of SCH527123 in animal models of liver, pancreatic and ovarian cancers has underscored its potential as an anti‑inflammatory and anti‑tumor agent. These findings suggest that targeting CXCR1/2 signaling may represent a viable approach for treating a broad range of malignancies. Furthermore, interest in SCH527123 as a potential treatment for COPD and asthma has suggested its potential applications beyond cancer therapy. Therefore, SCH527123 represents a new drug candidate with potential in the fields of inflammation and cancer. Although challenges remain in translating preclinical findings into clinical benefits, ongoing research and development efforts on using SCH527123 hold promise for improving the survival and quality of life of patients with these devastating diseases.
View Figures

Figure 1

After binding to CXCR2 receptor, IL-8
activates and migrates neutrophils, prompting white blood cells to
secrete a variety of cytokines, which promotes the development of
inflammation and aggravates inflammatory symptoms. CXCL, C-X-C
motif chemokine ligand; CXCR, C-X-C motif chemokine receptor.

Figure 2

IL-8 is involved in cancer
development through four pathways. (A) It promotes the
transformation of tumor cells into a more epidermal mesenchymal
phenotype. (B) It increases angiogenesis in the tumor and changes
the immune microenvironment by recruiting more invasive
immunosuppressive cells. (C) It increases the possibility of tumor
cell migration and invasion in vitro and metastasis in
vivo. (D) It recruits pre-tumor immune cells to inhibit the
anti-tumor immune response of cytotoxic immune cells. TME, tumor
microenvironment; CXCR, C-X-C motif chemokine receptor.

Figure 3

Chemical structures. (A) Lead
cyclobutenedione and (B) SCH527123.

Figure 4

(A) CXCL8/IL-8 binds to CXCR1/2 on
neutrophils, resulting in their activation and subsequent
accumulation at sites of inflammation. (B) SCH527123 blocks the
binding of CXCL8/IL-8 to CXCR1/2, thereby inhibiting neutrophil
activation. This inhibition further modulates neutrophil
transmigration towards chemokines containing the ELR motif,
preventing excessive inflammatory responses. CXCL, C-X-C motif
chemokine ligand; CXCR, C-X-C motif chemokine receptor.
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Copy and paste a formatted citation
Spandidos Publications style
Zhong J, He J, Xiong Y and Li M: Potential of CXCR1/2 as a target for the treatment of inflammation and cancer (Review). Exp Ther Med 30: 227, 2025.
APA
Zhong, J., He, J., Xiong, Y., & Li, M. (2025). Potential of CXCR1/2 as a target for the treatment of inflammation and cancer (Review). Experimental and Therapeutic Medicine, 30, 227. https://doi.org/10.3892/etm.2025.12977
MLA
Zhong, J., He, J., Xiong, Y., Li, M."Potential of CXCR1/2 as a target for the treatment of inflammation and cancer (Review)". Experimental and Therapeutic Medicine 30.6 (2025): 227.
Chicago
Zhong, J., He, J., Xiong, Y., Li, M."Potential of CXCR1/2 as a target for the treatment of inflammation and cancer (Review)". Experimental and Therapeutic Medicine 30, no. 6 (2025): 227. https://doi.org/10.3892/etm.2025.12977
Copy and paste a formatted citation
x
Spandidos Publications style
Zhong J, He J, Xiong Y and Li M: Potential of CXCR1/2 as a target for the treatment of inflammation and cancer (Review). Exp Ther Med 30: 227, 2025.
APA
Zhong, J., He, J., Xiong, Y., & Li, M. (2025). Potential of CXCR1/2 as a target for the treatment of inflammation and cancer (Review). Experimental and Therapeutic Medicine, 30, 227. https://doi.org/10.3892/etm.2025.12977
MLA
Zhong, J., He, J., Xiong, Y., Li, M."Potential of CXCR1/2 as a target for the treatment of inflammation and cancer (Review)". Experimental and Therapeutic Medicine 30.6 (2025): 227.
Chicago
Zhong, J., He, J., Xiong, Y., Li, M."Potential of CXCR1/2 as a target for the treatment of inflammation and cancer (Review)". Experimental and Therapeutic Medicine 30, no. 6 (2025): 227. https://doi.org/10.3892/etm.2025.12977
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