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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-B, 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.Contents 1. Introduction 2. CXCL1 expression, sources and signaling in TNBC 3. Upstream regulation of CXCL1 signaling 4. Downstream regulation of CXCL1 signaling 5. Role of CXCL1 in TNBC progression and the TME 6. Therapeutic potential of targeting CXCL1 signaling in TNBC 7. Potential therapeutic agents targeting CXCL1 8. Potential resistance mechanisms to CXCL1-targeted therapy 9. Challenges for clinical translation 10.Conclusion
Sayegh et al. (Tue,) studied this question.