ArticleGenes & development2015
Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 119 citations in OpenAlex.
- Safety and preliminary efficacy of adding tocilizumab to cisplatin/docetaxel for the treatment of locally advanced triple-negative breast cancer patients: prospective phase 1/2 clinical trial.Scientific reports · 2026Trial
- Phase I/II trial of ruxolitinib in combination with trastuzumab in metastatic HER2 positive breast cancer.Breast cancer research and treatment · 2021Trial
- Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017 · on this mapTrial
- Impact of organic pollutants on phenotype and gene expression in human breast cancer cells.Journal of applied toxicology : JAT · 2026Article
- The double-edged sword of SASP in breast cancer: from tumor suppression to progression and therapy resistance.Frontiers in oncology · 2026Review
- Secoisolariciresinol diglucoside alleviates inflammatory injury in osteoarthritis chondrocytes through ERBB2-associated JAK2/STAT3 signaling: network pharmacology and experimental validation.Frontiers in immunology · 2026Article
- Genetic and immune regulatory links between inflammatory bowel disease and breast cancer involving the JAK STAT PD L1 axis.Discover oncology · 2025Article
- Co-Inhibition of PARP and STAT3 as a Promising Approach for Triple-Negative Breast Cancer.Biomolecules · 2025Article
- E2F1 activates breast stromal fibroblasts and promotes their paracrine pro-carcinogenic effects.Scientific reports · 2025Article
- Article
- Identifying the mechanism of polysaccharopeptide against breast cancer based on network pharmacology and experimental verification.BMC cancer · 2024Article
- Proteomic Assessment of SKBR3/HER2+ Breast Cancer Cellular Response to Lapatinib and Investigational Ipatasertib Kinase Inhibitors.bioRxiv : the preprint server for biology · 2024Article
- S100A8/A9 predicts response to PIM kinase and PD-1/PD-L1 inhibition in triple-negative breast cancer mouse models.Communications medicine · 2024Article
- Navigating the Cytokine Seas: Targeting Cytokine Signaling Pathways in Cancer Therapy.International journal of molecular sciences · 2024Review
- Searching for Essential Genes and Targeted Drugs Common to Breast Cancer and Osteoarthritis.Combinatorial chemistry & high throughput screening · 2024Article
- Proteomic assessment of SKBR3/HER2+ breast cancer cellular response to Lapatinib and investigational Ipatasertib kinase inhibitors.Frontiers in pharmacology · 2024Article
- S100A8/A9 as a risk factor for breast cancer negatively regulated by DACH1.Biomarker research · 2023Article
- ARF6 promotes hepatocellular carcinoma proliferation through activating STAT3 signaling.Cancer cell international · 2023Article
- A Transcriptome-Based Precision Oncology Platform for Patient-Therapy Alignment in a Diverse Set of Treatment-Resistant Malignancies.Cancer discovery · 2023Article
- Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer.Signal transduction and targeted therapy · 2023Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
HER2-positive (HER2(+)) breast adenocarcinomas are a heterogeneous group in which hormone receptor (HR) status influences therapeutic decisions and patient outcome. By combining genome-wide RNAi screens with regulatory network analysis, we identified STAT3 as a critically activated master regulator of HR(-)/HER2(+) tumors, eliciting tumor dependency in these cells. Mechanistically, HR(-)/HER2(+) cells secrete high levels of the interleukin-6 (IL-6) cytokine, inducing the activation of STAT3, which in turn promotes a second autocrine stimulus to increase S100A8/9 complex (calprotectin) production and secretion. Increased calprotectin levels activate signaling pathways involved in proliferation and resistance. Importantly, we demonstrated that inhibition of the IL-6-Janus kinase 2 (JAK2)-STAT3-calprotectin axis with FDA-approved drugs, alone and in combination with HER2 inhibitors, reduced the tumorigenicity of HR(-)/HER2(+) breast cancers, opening novel targeted therapeutic opportunities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.