ArticleOncogenesis2021
IL-6 promotes drug resistance through formation of polyploid giant cancer cells and stromal fibroblast reprogramming.
Article in Oncogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Inflamed Yet Immune-Evasive? A Transcriptomic Meta-Analysis Identifies Conserved Inflammatory, Developmental, and Neuronal Signatures Associated with Polyploid Giant Cancer Cells.International journal of molecular sciences · 2026Pooled it
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- RAC1 signaling in polyploid giant cancer cells: Implications for tumorigenesis and therapy resistance.Cancer letters · 2026Review
- Tetraploids or polyploid giants: who is truly dangerous?Trends in cell biology · 2026Review
- Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.Biology direct · 2026Review
- Clinical Implications of Polyploid Giant Cancer Cells in Solid Tumors: Biology, Diagnosis, and Therapeutic Considerations.Cancers · 2026Review
- DCLK1 regulates stemness and IL-6/STAT3-dependent metastatic niche formation in chemoresistant ovarian cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Cellular senescence in lung cancer immune microenvironment and senotherapeutic opportunities.iScience · 2026Review
- Etiology of polyploid giant cancer cells: a new frontier in cancer biology.Cancer cell international · 2026Review
- Cross-talk between cancer-associated fibroblasts and dormant cancer cells: current status and promising therapeutic potential.Cancer cell international · 2025Review
- Modelling the monstrosities: experimental and computational systems for studying polyploid giant cancer cells.Expert reviews in molecular medicine · 2025Review
- Unscheduled polyploidy synergizes with oncogenic mutations to enhance genome instability and tumorigenesis.Cancer letters · 2025Article
- Polyploid giant cancer cells (PGCC): short-term return to multicellularity.Biological research · 2025Article
- Aurora Kinase A inhibitor alisertib failed to exert its efficacy on TNBC cells due to consequential enrichment of polyploid giant cancer cells (PGCCs).Discover oncology · 2025Article
- Role of interleukin-6 in resistance to tumor therapy.Discover oncology · 2025Review
- Persistent accumulation of therapy-induced senescent cells: an obstacle to long-term cancer treatment efficacy.International journal of oral science · 2025Review
- Leveraging chromatin packing domains to target chemoevasion in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Global modulation of gene expression and transcriptome size in aneuploid combinations of maize.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Epithelial-mesenchymal transition orchestrates tumor microenvironment: current perceptions and challenges.Journal of translational medicine · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
To understand the role of polyploid giant cancer cells (PGCCs) in drug resistance and disease relapse, we examined the mRNA expression profile of PGCCs following treatment with paclitaxel in ovarian cancer cells. An acute activation of IL-6 dominated senescence-associated secretory phenotype lasted 2-3 weeks and declined during the termination phase of polyploidy. IL-6 activates embryonic stemness during the initiation of PGCCs and can reprogram normal fibroblasts into cancer-associated fibroblasts (CAFs) via increased collagen synthesis, activation of VEGF expression, and enrichment of CAFs and the GPR77 + /CD10 + fibroblast subpopulation. Blocking the IL-6 feedback loop with tocilizumab or apigenin prevented PGCC formation, attenuated embryonic stemness and the CAF phenotype, and inhibited tumor growth in a patient-derived xenograft high-grade serous ovarian carcinoma model. Thus, IL-6 derived by PGCCs is capable of reprogramming both cancer and stromal cells and contributes to the evolution and remodeling of cancer. Targeting IL-6 in PGCCs may represent a novel approach to combating drug resistance.
Identifiers
What OpenQuestion holds
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.