ArticleNeoplasia (New York, N.Y.)2017
Novel C-Terminal Heat Shock Protein 90 Inhibitors (KU711 and Ku757) Are Effective in Targeting Head and Neck Squamous Cell Carcinoma Cancer Stem cells.
Article in Neoplasia (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- miRNAs, Mesenchymal Stromal Cells and Major Neoplastic and Inflammatory Skin Diseases: A Page Being Written: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Repurposing T-type calcium channel blocker lomerizine as a therapeutic strategy for glioblastoma.JCI insight · 2026Article
- Review
- C-Terminal Hsp90 Inhibitors Overcome MEK and BRAF Inhibitor Resistance in Melanoma.Journal of cellular and molecular medicine · 2025Article
- Cancer Stem Cells in Oral Squamous Cell Carcinoma: A Narrative Review on Experimental Characteristics and Methodological Challenges.Biomedicines · 2024Review
- Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.Journal of hematology & oncology · 2024Review
- Targeting cancer stem cells as a strategy for reducing chemotherapy resistance in head and neck cancers.Journal of cancer research and clinical oncology · 2023Review
- circSLC4A7 accelerates stemness and progression of gastric cancer by interacting with HSP90 to activate NOTCH1 signaling pathway.Cell death & disease · 2023Article
- A curcumin analogue GO-Y030 depletes cancer stem cells by inhibiting the interaction between the HSP70/HSP40 complex and its substrates.FEBS open bio · 2023Article
- Recent advances toward the development of Hsp90 C-terminal inhibitors.Bioorganic & medicinal chemistry letters · 2023Review
- Cancer stem cells of head and neck squamous cell carcinoma; distance towards clinical application; a systematic review of literature.American journal of cancer research · 2023Review
- HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review).Oncology reports · 2023Review
- A novel C-terminal Hsp90 inhibitor KU758 synergizes efficacy in combination with BRAF or MEK inhibitors and targets drug-resistant pathways in BRAF-mutant melanomas.Melanoma research · 2021Article
- Advancement in Cancer Stem Cell Biology and Precision Medicine-Review Article Head and Neck Cancer Stem Cell Plasticity and the Tumor Microenvironment.Frontiers in cell and developmental biology · 2021Review
- Article
- Combinatorial Strategies to Target Molecular and Signaling Pathways to Disarm Cancer Stem Cells.Frontiers in oncology · 2021Review
- Review
- Suppression of Esophageal Cancer Stem-like Cells by SNX-2112 Is Enhanced by STAT3 Silencing.Frontiers in pharmacology · 2020Article
- Identification and chemoresistance of cancer stem cells in HPV-negative oropharyngeal cancer.Oncology letters · 2020Article
- Old and New Approaches to Target the Hsp90 Chaperone.Current cancer drug targets · 2020Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Advanced head and neck squamous cell carcinoma (HNSCC) remains a therapeutic challenge due to the development of therapy resistance. Several studies have implicated the development of cancer stem cells as a possible mechanism for therapy resistance in HNSCC. Heat shock protein 90's (Hsp90's) molecular chaperone function is implicated in pathways of resistance in HNSCC. Therefore, in the present study, we investigated the efficacy of novel C-terminal Hsp90 inhibitors (KU711 and KU757) in targeting HNSCC cancer stem cells (CSCs). Treatment of HNSCC human cell lines MDA1986, UMSCC 22B, and UMSCC 22B cisplatin-resistant cells with the KU compounds indicated complete blockage of self-renewal for the resistant and parent cell lines starting from 20 μM KU711 and 1 μM KU757. Dose-dependent decrease in the cancer stem cell markers CD44, ALDH, and CD44/ALDH double-positive cells was observed for all cell lines after treatment with KU711 and KU757. When cells were treated with either drug, migration and invasion were downregulated greater than 90% even at the lowest concentrations of 20 μM KU711 and 1 μM KU757. Western blot showed >90% reduction in client protein "stemness" marker BMI-1 and mesenchymal marker vimentin, as well as increase in epithelial marker E-cadherin for both cell lines, indicating epithelial to mesenchymal transition quiescence. Several CSC-mediated miRNAs that play a critical role in HNSCC therapy resistance were also downregulated with KU treatment. In vivo, KU compounds were effective in decreasing tumor growth with no observed toxicity. Taken together, these results indicate that KU compounds are effective therapeutics for targeting HNSCC CSCs.
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