Cytokine Signaling Dynamics in Breast Cancer: From Tumor Initiation to Progression and Therapy Resistance

Breast cancer remains one of the most prevalent malignancies worldwide, with approximately 2.3 million new cases diagnosed annually. Cytokines - small secreted proteins mediating intercellular communication - play central roles in orchestrating the tumor microenvironment (TME), modulating immune infiltration, and regulating tumor cell behavior. Dysregulated cytokine signalling is implicated at every stage of breast cancer pathogenesis, from pre-malignant transformation and primary tumor growth to distant metastasis. Despite considerable advances in targeted therapies and immunotherapies, a substantial proportion of patients develop therapy resistance, partly driven by dynamic remodeling of cytokine networks. A comprehensive understanding of cytokine signalling dynamics is therefore essential to improve treatment outcomes across all breast cancer molecular subtypes.
This Research Topic aims to consolidate current knowledge and present emerging discoveries on the multifaceted roles of cytokines in breast cancer biology. We seek to address key unresolved questions: How do specific cytokine axes initiate oncogenic transformation? What cytokine-driven mechanisms sustain tumor progression and promote metastasis? How do tumors exploit cytokine signalling to evade therapeutic interventions, including endocrine therapy, chemotherapy, targeted therapy, and immune checkpoint blockade? By bringing together original research articles, systematic reviews, and translational perspectives, this collection will provide a comprehensive resource for researchers, clinicians, and drug developers. Ultimately, we aim to identify actionable cytokine-based biomarkers and therapeutic targets that can inform the next generation of breast cancer treatments. We also welcome contributions exploring the prevalence and underlying biological mechanisms driving changes in molecular characteristics of breast cancer following neoadjuvant therapy, particularly through comparative analyses of diagnostic biopsy samples and residual disease at surgery.
We welcome original research, reviews, and perspectives covering: cytokine receptor signalling pathways in breast cancer and stromal cells; interleukin, chemokine, and interferon networks in the TME; cytokine-mediated immune evasion and immunotherapy resistance; cytokine roles in endocrine, HER2-targeted, CDK4/6 inhibitor, and antibody-drug conjugate resistance; breast cancer subtype-specific cytokine signatures; single-cell and spatial transcriptomics approaches to cytokine mapping; and translational studies linking cytokine biomarkers to clinical outcomes. Studies on understudied subtypes (triple-negative, inflammatory breast cancer) and clinical-translational work are particularly encouraged. Both basic and applied science manuscripts are considered.
Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases, which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.