ArticleJCI insight2018
IL-6 mediates platinum-induced enrichment of ovarian cancer stem cells.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 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
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Inexpensive Systemic Inflammatory Biomarkers in Ovarian Cancer: An Umbrella Systematic Review of 17 Prognostic Meta-Analyses.Frontiers in oncology · 2021Pooled it
- Olaparib, durvalumab, and cyclophosphamide, and a prognostic blood signature in platinum-sensitive ovarian cancer: the randomized phase 2 SOLACE2 trial.Nature communications · 2025Trial
- A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- DNA Methyltransferase Inhibition Prevents Platinum-Induced Ovarian Cancer Stem Cell Enrichment.Cancer research communications · 2026Article
- ESM1 drives cisplatin resistance and ferroptosis resistance via ERBB2/FAK/SRC/HSPB1/NF-κB signaling in ovarian cancer.iScience · 2026Article
- Chemotherapy Enrichment of ID Family Expression Is Associated with IL-6 Signaling in Ovarian Cancer.Cancers · 2026Article
- Two cycles of chemotherapy modulate itaconic acid levels via ATF3/TET2/NF-κB pathways in ovarian cancer among Han Chinese women.Journal of ovarian research · 2026Article
- Targeting cancer stem cells predicts response and reverses chemoresistance in ascites-derived ovarian cancer organoids.BMC medicine · 2026Article
- Inflammatory milieu and role of epigenetic modifications in high-grade serous ovarian cancer.Clinical epigenetics · 2026Review
- D-dimer as a more effective marker for detecting thrombosis in patients with ovarian clear cell carcinoma compared with high-grade serous carcinoma.Molecular and clinical oncology · 2026Article
- Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies.Oncology research · 2026Review
- NanoString profiling of DNA repair and apoptosis genes in testicular germ cell tumours with divergent chemotherapy outcomes.Therapeutic advances in medical oncology · 2026Article
- Fueling the Seed: Growth Factors and Cytokines Driving Cancer Stem Cells in Gynecological Malignancies.International journal of molecular sciences · 2025Review
- Role of interleukin-6 in resistance to tumor therapy.Discover oncology · 2025Review
- IL-6R expression is an independent prognostic factor in high-grade serous ovarian cancer.BJC reports · 2025Article
- Glucosylceramide Synthase, a Key Enzyme in Sphingolipid Metabolism, Regulates Expression of Genes Accounting for Cancer Drug Resistance.International journal of molecular sciences · 2025Article
- Review
- A comprehensive overview of ovarian cancer stem cells: correlation with high recurrence rate, underlying mechanisms, and therapeutic opportunities.Molecular cancer · 2025Review
- Chromatin Organization Governs Transcriptional Response and Plasticity of Cancer Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Harnessing the interaction between redox signaling and senescence to restrain tumor drug resistance.Frontiers in cell and developmental biology · 2025Review
20 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
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In high-grade serous ovarian cancer (OC), chemotherapy eliminates the majority of tumor cells, leaving behind residual tumors enriched in OC stem cells (OCSC). OCSC, defined as aldehyde dehydrogenase-positive (ALDH+), persist and contribute to tumor relapse. Inflammatory cytokine IL-6 is elevated in residual tumors after platinum treatment, and we hypothesized that IL-6 plays a critical role in platinum-induced OCSC enrichment. We demonstrate that IL-6 regulates stemness features of OCSC driven by ALDH1A1 expression and activity. We show that platinum induces IL-6 secretion by cancer-associated fibroblasts in the tumor microenvironment, promoting OCSC enrichment in residual tumors after chemotherapy. By activating STAT3 and upregulating ALDH1A1 expression, IL-6 treatment converted non-OCSC to OCSC. Having previously shown altered DNA methylation in OCSC, we show here that IL-6 induces DNA methyltransferase 1 (DNMT1) expression and the hypomethylating agent (HMA) guadecitabine induced differentiation of OCSC and reduced - but did not completely eradicate - OCSC. IL-6 neutralizing antibody (IL-6-Nab) combined with HMA fully eradicated OCSC, and the combination blocked IL-6/IL6-R/pSTAT3-mediated ALDH1A1 expression and eliminated OCSC in residual tumors that persisted in vivo after chemotherapy. We conclude that IL-6 signaling blockade combined with an HMA can eliminate OCSC after platinum treatment, supporting this strategy to prevent tumor recurrence after standard chemotherapy.
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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.