ArticleBritish journal of cancer2010
Novel HSP90 inhibitors, NVP-AUY922 and NVP-BEP800, radiosensitise tumour cells through cell-cycle impairment, increased DNA damage and repair protraction.
Article in British journal of cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 85 citations in OpenAlex.
- Radiosensitization of NET cells by HSP90 inhibitor ganetespib is mediated through pleiotropic stress responses.EJNMMI research · 2025Article
- Overcoming cancer drug resistance through small-molecule targeting of HSP90 and HSP70.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Compound Taxus exerts marked anti-tumor activity and radiosensitization effect on hepatocellular carcinoma cells.Heliyon · 2024Article
- Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.Cells · 2022Review
- Disruption of DNA Repair and Survival Pathways through Heat Shock Protein Inhibition by Onalespib to Sensitize Malignant Gliomas to Chemoradiation Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- TAS-116 (pimitespib), a heat shock protein 90 inhibitor, shows efficacy in preclinical models of adult T-cell leukemia.Cancer science · 2022Article
- A Low Membrane Hsp70 Expression in Tumor Cells With Impaired Lactate Metabolism Mediates Radiosensitization by NVP-AUY922.Frontiers in oncology · 2022Article
- Potential Molecular Targets in the Setting of Chemoradiation for Esophageal Malignancies.Journal of the National Cancer Institute · 2021Review
- Article
- Cooperative treatment effectiveness of ATR and HSP90 inhibition in Ewing's sarcoma cells.Cell & bioscience · 2021Article
- HSP90 inhibitor NVP-BEP800 affects stability of SRC kinases and growth of T-cell and B-cell acute lymphoblastic leukemias.Blood cancer journal · 2021Article
- Understanding the Hsp90Molecules (Basel, Switzerland) · 2020Article
- Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?International journal of molecular sciences · 2019Review
- Radiosensitization of HSF-1 Knockdown Lung Cancer Cells by Low Concentrations of Hsp90 Inhibitor NVP-AUY922.Cells · 2019Article
- 177Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition.Endocrine-related cancer · 2019Article
- MEK-inhibitor PD184352 enhances the radiosensitizing effect of the Hsp90 inhibitor NVP-AUY922: the role of cell type and drug-irradiation schedule.Oncotarget · 2018Article
- The HSP90 inhibitor NVP-AUY922 inhibits growth of HER2 positive and trastuzumab-resistant breast cancer cells.Investigational new drugs · 2018Article
- Identification of Novel Response and Predictive Biomarkers to Hsp90 Inhibitors Through Proteomic Profiling of Patient-derived Prostate Tumor Explants.Molecular & cellular proteomics : MCP · 2018Article
- Heat shock proteins and DNA repair mechanisms: an updated overview.Cell stress & chaperones · 2018Review
- Profiles of Radioresistance Mechanisms in Prostate Cancer.Critical reviews in oncogenesis · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHeat-shock protein 90 (Hsp90) has a crucial role in both the stabilisation and regulation of various proteins, including those related to radioresistance. Inhibition of Hsp90 may therefore provide a strategy for enhancing the radiosensitivity of tumour cells. This study explores the responses of four tumour cell lines (A549, GaMG, HT 1080 and SNB19) to combined treatment with ionising radiation (IR) and two novel inhibitors of Hsp90, NVP-AUY922 and NVP-BEP800. The techniques used included cell and colony counts, expression of Hsp90, Hsp70, Akt, survivin, cleaved caspase 3, p53, cell-cycle progression and associated proteins. DNA damage was analysed by histone gammaH2AX and Comet assays.
resultsWe found that NVP-AUY922 and NVP-BEP800 enhanced radiosensitivity in all tested cell lines. In contrast, only two cell lines (HT 1080 and GaMG) exhibited an increased rate of apoptosis after drug pretreatment, as revealed by western blot. In all tested cell lines, the expression of histone gammaH2AX, a marker of DNA double-strand breaks, after combined drug-IR treatment was higher and its decay rate was slower than those after each single treatment modality. Drug-IR treatment also resulted in impaired cell-cycle progression, as indicated by S-phase depletion and G2/M arrest. In addition, the cell cycle-associated proteins, Cdk1 and Cdk4, were downregulated after Hsp90 inhibition.
interpretationThese findings show that the novel inhibitors of Hsp90 can radiosensitise tumour cell lines of different entities through destabilisation and depletion of several Hsp90 client proteins, thus causing the depletion of S phase and G2/M arrest, increased DNA damage and repair protraction and, to some extent, apoptosis. The results might have important implications for the radiotherapy of solid tumours.
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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.