ArticleOncotarget2013
Targeting HSF1 sensitizes cancer cells to HSP90 inhibition.
Article in Oncotarget, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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
36 citing papers in PubMed, 59 citations in OpenAlex.
- Pharmacodynamic and Clinical Results from a Phase I/II Study of the HSP90 Inhibitor Onalespib in Combination with Abiraterone Acetate in Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- A guide to heat shock factors as multifunctional transcriptional regulators.The FEBS journal · 2025Review
- Review
- Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.Cells · 2022Review
- Review
- Quantitative and multiplexed chemical-genetic phenotyping in mammalian cells with QMAP-Seq.Nature communications · 2020Article
- HSF1: Primary Factor in Molecular Chaperone Expression and a Major Contributor to Cancer Morbidity.Cells · 2020Review
- Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1.Experimental & molecular medicine · 2020Article
- Radiosensitization of HSF-1 Knockdown Lung Cancer Cells by Low Concentrations of Hsp90 Inhibitor NVP-AUY922.Cells · 2019Article
- Article
- Role of the heat shock protein family in bone metabolism.Cell stress & chaperones · 2018Review
- Emerging Cancer Therapeutic Targets in Protein Homeostasis.The AAPS journal · 2018Article
- A Futile Battle? Protein Quality Control and the Stress of Aging.Developmental cell · 2018Review
- The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Genetic polymorphism and expression of HSF1 gene is significantly associated with breast cancer in Saudi females.PloS one · 2018Article
- Histone deacetylase activity mediates acquired resistance towards structurally diverse HSP90 inhibitors.Molecular oncology · 2017Article
- Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90.Cancers · 2016Article
- Discovery of 4,6-disubstituted pyrimidines as potent inhibitors of the heat shock factor 1 (HSF1) stress pathway and CDK9.MedChemComm · 2016Article
- Article
- X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular chaperone heat shock protein 90 (HSP90) facilitates the appropriate folding of various oncogenic proteins and is necessary for the survival of some cancer cells. HSP90 is therefore an attractive drug target, but the efficacy of HSP90 inhibitor may be limited by HSP90 inhibition induced feedback mechanisms. Through pooled RNA interference screens, we identified that heat shock factor 1(HSF1) is a sensitizer of HSP90 inhibitor. A striking combinational effect was observed when HSF1 knockdown plus with HSP90 inhibitors treatment in various cancer cell lines and tumor mouse models. Interestingly, HSF1 is highly expressed in hepatocellular carcinoma (HCC) patient samples and HCC is sensitive to combinational treatment, indicating a potential indication for the combinational treatment. To understand the mechanism of the combinational effect, we identified that a HSF1-target gene DEDD2 is involved in attenuating the effect of HSP90 inhibitors. Thus, the transcriptional activities of HSF1 induced by HSP90 inhibitors provide a feedback mechanism of limiting the HSP90 inhibitor's activity, and targeting HSF1 may provide a new avenue to enhance HSP90 inhibitors activity in human cancers.
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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.