ArticleOncotarget2016
Interleukin-6 expression contributes to lapatinib resistance through maintenance of stemness property in HER2-positive breast cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Prognostic Relevance of Inflammatory Cytokines Il-6 and TNF-Alpha in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.Current oncology (Toronto, Ont.) · 2025Pooled it
- Ebastine targets HER2/HER3 signaling and cancer stem cell traits to overcome trastuzumab resistance in HER2‑positive breast cancer.International journal of molecular medicine · 2026Article
- Article
- The Regulatory Role of CTCF in IL6 Gene Transcription Assessed in Breast Cancer Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2025Article
- STAT3: Key targets of growth-promoting receptor positive breast cancer.Cancer cell international · 2024Review
- Self-Renewal Inhibition in Breast Cancer Stem Cells: Moonlight Role of PEDF in Breast Cancer.Cancers · 2023Article
- Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition.International journal of molecular sciences · 2023Review
- miR-221 confers lapatinib resistance by negatively regulating p27Cancer science · 2021Article
- HER2-targeted antibody-drug conjugate induces host immunity against cancer stem cells.Cell chemical biology · 2021Article
- The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer.Frontiers in oncology · 2021Review
- Pim1 Kinase Inhibitors Exert Anti-Cancer Activity Against HER2-Positive Breast Cancer Cells Through Downregulation of HER2.Frontiers in pharmacology · 2021Article
- An organotin indomethacin derivative inhibits cancer cell proliferation and synergizes the antiproliferative effects of lapatinib in breast cancer cells.American journal of cancer research · 2020Article
- Contribution of synergism between PHF8 and HER2 signalling to breast cancer development and drug resistance.EBioMedicine · 2020Article
- Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer.Frontiers in oncology · 2020Review
- Pleiotropic Effects of Epithelial Mesenchymal Crosstalk on Head and Neck Cancer: EMT and beyond.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2019Article
- Challenges and future of precision medicine strategies for breast cancer based on a database on drug reactions.Bioscience reports · 2019Review
- Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation.International journal of molecular sciences · 2019Article
- HER2 in stemness and epithelial-mesenchymal plasticity of breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- IL-6 Promotes Cancer Stemness and Oncogenicity in U2OS and MG-63 Osteosarcoma Cells by Upregulating the OPN-STAT3 Pathway.Journal of Cancer · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lapatinib is an inhibitor of human epidermal growth factor receptor 2 (HER2), which is overexpressed in 20-25% of breast cancers. Clinically, lapatinib has shown promising benefits for HER2-positive breast cancer patients; however, patients eventually acquire resistance, limiting its long-term use. In a previous study, we found that interleukin-6 (IL-6) production was increased in acquired lapatinib-resistant HER2-positive breast cancer cells. In the present study, we confirmed that lapatinib-resistant cells had elevated IL-6 expression and also maintained both stemness population and property. The increase in IL-6 was required for stemness property maintenance, which was mediated primarily through the activation of signal transducer and activator of transcription 3 (STAT3). Blocking IL-6 activity reduced spheroid formation, cell viability and subsequently overcame lapatinib resistance, whereas stimulation of IL-6 rendered parental cells more resistant to lapatinib-induced cytotoxicity. These results point to a novel mechanism underlying lapatinib resistance and provide a potential strategy to overcome resistance via IL-6 inhibition.
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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.