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Review Open Access

CXCL1 in triple‑negative breast cancer: Mechanisms, challenges, and therapeutic opportunities (Review)

  • Authors:
    • Hiba Al Sayegh
    • Zahraa Assi
    • Amjad Kanaan
    • Mirvat El Sibai
  • View Affiliations / Copyright

    Affiliations: Department of Biological Sciences, Lebanese American University, Beirut 1102‑2801, Lebanon, Department of Biomedical Sciences, School of Medicine, University of Balamand, Beirut 1100‑2807, Lebanon
    Copyright: © Al Sayegh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 86
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    Published online on: March 3, 2026
       https://doi.org/10.3892/or.2026.9091
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Abstract

Triple negative breast cancer (TNBC) is an aggressive BC subtype with limited therapeutic options and poor clinical outcomes. This subtype accounts for 15‑20% of all BC cases and contributes to nearly 40% of BC mortalities. The chemokine C‑X‑C motif ligand 1 (CXCL1) is a key player in TNBC progression through several signaling pathways, including NF‑κB, MAPK and related cascades. CXCL1 contributes to tumor growth, metastasis, immune modulation and resistance to therapy, however its role and therapeutic potential in TNBC has not been comprehensively described. The present review aimed to summarize CXCL1 biology in TNBC, with a focus on its prognostic relevance, role in the tumor microenvironment and potential as a therapeutic target, as well as emerging strategies aimed at modulating CXCL1 signaling. However, challenges remain in translating these findings into clinical application, including incomplete understanding of certain molecular mechanisms underlying CXCL1 function, unclear prognostic value, the need for validation of potential inhibitors in large and diverse cohorts and the lack of well‑designed clinical trials testing CXCL1‑targeted approaches. Addressing these challenges through rigorous preclinical work and carefully designed clinical trials is key to define the true therapeutic potential of CXCL1 in TNBC to advance precision medicine strategies and enhance clinical outcomes in patients with TNBC.
View Figures

Figure 1

Upstream regulation of CXCL1
expression via NF-κB. IκB is phosphorylated by IKK, which marks it
for ubiquitination and leads to its degradation, enabling NF-κB to
enter the nucleus and activate transcription of CXCL1. IL-17 and
TNF-α activate NF κB signaling. NF-κB may also be induced by the
transcription factor FOXC1 in triple-negative breast cancer cells.
Created using Canva.com. Ub, Ubiquitin; IKK, IκB kinase.

Figure 2

EVs and TAM/CXCL1/PD-L1
pathways.CXCR2-independent pathway. Chemotherapeutic agents such as
paclitaxel induce the release of CXCL1-enriched EVs from apoptotic
TNBC cells. EVs are phagocyted by macrophages, then the CXCL1 cargo
within them is released into the cytoplasm. This promotes EED
expression and its nuclear translocation. EED binds to the PD-L1
promoter, enhancing PD-L1 transcription. This pathway drives TNBC
tumor growth, M2 TAM polarization, immune evasion and
chemoresistance. CXCR2-mediated pathway. CXCL1 secreted by M2
macrophages in the TME promotes PD-L1 upregulation in TNBC via
activation of the CXCR2-mediated PI3K/AKT/NF-κB signaling pathway.
This pathway contributes to immune evasion. Created using Microsoft
PowerPoint 2016. EV, extracellular vesicle; TAM, tumor-associated
macrophage; TNBC, triple-negative breast cancer; EED, ectoderm
development protein.
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Copy and paste a formatted citation
Spandidos Publications style
Al Sayegh H, Assi Z, Kanaan A and El Sibai M: CXCL1 in triple‑negative breast cancer: Mechanisms, challenges, and therapeutic opportunities (Review). Oncol Rep 55: 86, 2026.
APA
Al Sayegh, H., Assi, Z., Kanaan, A., & El Sibai, M. (2026). CXCL1 in triple‑negative breast cancer: Mechanisms, challenges, and therapeutic opportunities (Review). Oncology Reports, 55, 86. https://doi.org/10.3892/or.2026.9091
MLA
Al Sayegh, H., Assi, Z., Kanaan, A., El Sibai, M."CXCL1 in triple‑negative breast cancer: Mechanisms, challenges, and therapeutic opportunities (Review)". Oncology Reports 55.5 (2026): 86.
Chicago
Al Sayegh, H., Assi, Z., Kanaan, A., El Sibai, M."CXCL1 in triple‑negative breast cancer: Mechanisms, challenges, and therapeutic opportunities (Review)". Oncology Reports 55, no. 5 (2026): 86. https://doi.org/10.3892/or.2026.9091
Copy and paste a formatted citation
x
Spandidos Publications style
Al Sayegh H, Assi Z, Kanaan A and El Sibai M: CXCL1 in triple‑negative breast cancer: Mechanisms, challenges, and therapeutic opportunities (Review). Oncol Rep 55: 86, 2026.
APA
Al Sayegh, H., Assi, Z., Kanaan, A., & El Sibai, M. (2026). CXCL1 in triple‑negative breast cancer: Mechanisms, challenges, and therapeutic opportunities (Review). Oncology Reports, 55, 86. https://doi.org/10.3892/or.2026.9091
MLA
Al Sayegh, H., Assi, Z., Kanaan, A., El Sibai, M."CXCL1 in triple‑negative breast cancer: Mechanisms, challenges, and therapeutic opportunities (Review)". Oncology Reports 55.5 (2026): 86.
Chicago
Al Sayegh, H., Assi, Z., Kanaan, A., El Sibai, M."CXCL1 in triple‑negative breast cancer: Mechanisms, challenges, and therapeutic opportunities (Review)". Oncology Reports 55, no. 5 (2026): 86. https://doi.org/10.3892/or.2026.9091
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