ArticleCancer research2015
Adaptive Upregulation of EGFR Limits Attenuation of Tumor Growth by Neutralizing IL6 Antibodies, with Implications for Combined Therapy in Ovarian Cancer.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Deciphering oxidative stress contributions in vestibular schwannoma: A bioinformatics approach to novel therapeutic pathways.PloS one · 2025Article
- Neutrophils in the premetastatic niche: key functions and therapeutic directions.Molecular cancer · 2024Review
- Stroma-derived miR-214 coordinates tumor dissemination.Journal of experimental & clinical cancer research : CR · 2023Article
- Modelling TGFβR and Hh pathway regulation of prognostic matrisome molecules in ovarian cancer.iScience · 2021Article
- A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion.iScience · 2021Article
- Carcinogenesis: Failure of resolution of inflammation?Pharmacology & therapeutics · 2021Review
- Characteristics of pre-metastatic niche: the landscape of molecular and cellular pathways.Molecular biomedicine · 2021Review
- Autocrine IL-6/STAT3 signaling aids development of acquired drug resistance in Group 3 medulloblastoma.Cell death & disease · 2020Article
- Resolution of eicosanoid/cytokine storm prevents carcinogen and inflammation-initiated hepatocellular cancer progression.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Feedback activation of EGFR is the main cause for STAT3 inhibition-irresponsiveness in pancreatic cancer cells.Oncogene · 2020Article
- Chitosan-coated liposomes loaded with butyric acid demonstrate anticancer and anti-inflammatory activity in human hepatoma HepG2 cells.Oncology reports · 2019Article
- Suppression of chemotherapy-induced cytokine/lipid mediator surge and ovarian cancer by a dual COX-2/sEH inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- IL-6 mediates platinum-induced enrichment of ovarian cancer stem cells.JCI insight · 2018Article
- Molecular cross-talk of IL-6 in tumors and new progress in combined therapy.Thoracic cancer · 2018Review
- Effects of general anesthesia with or without epidural block on tumor metastasis and mechanisms.Oncology letters · 2018Article
- TRAF6 regulates EGF-induced cell transformation and cSCC malignant phenotype through CD147/EGFR.Oncogenesis · 2018Article
- CCL2/CCL5 secreted by the stroma induce IL-6/PYK2 dependent chemoresistance in ovarian cancer.Molecular cancer · 2018Article
- Article
- A loop of cancer-stroma-cancer interaction promotes peritoneal metastasis of ovarian cancer via TNFα-TGFα-EGFR.Oncogene · 2017Article
- IL6-mediated inflammatory loop reprograms normal to epithelial-mesenchymal transitionHepatology (Baltimore, Md.) · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Excess production of the proinflammatory IL6 has both local and systemic tumor-promoting activity in many cancers, including ovarian cancer. However, treatment of advanced ovarian cancer patients with a neutralizing IL6 antibody yielded little efficacy in a previous phase II clinical trial. Here, we report results that may explain this outcome, based on the finding that neutralizing antibodies to IL6 and STAT3 inhibition are sufficient to upregulate the EGFR pathway in high-grade serous and other ovarian cancer cells. Cell treatment with the EGFR inhibitor gefitinib abolished upregulation of the EGFR pathway. Combining neutralizing IL6 antibodies and gefitinib inhibited malignant cell growth in 2D and 3D culture. We found that ErbB-1 was localized predominantly in the nucleus of ovarian cancer cells examined, contrasting with plasma membrane localization in lung cancer cells. Treatment with anti-IL6, gefitinib, or their combination all led to partial restoration of ErbB-1 on the plasma membrane. In vivo experiments confirmed the effects of IL6 inhibition on the EGFR pathway and the enhanced activity of a combination of anti-IL6 antibodies and gefitinib on malignant cell growth. Taken together, our results offer a preclinical rationale to combine anti-IL6 and gefitinib to treat patients with advanced stage ovarian cancer.
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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.