ArticleCancer biology & therapy2015
The HSP90 inhibitor alvespimycin enhances the potency of telomerase inhibition by imetelstat in human osteosarcoma.
Article in Cancer biology & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- Unveiling the Impact of Copper Metabolism on Epithelial-Mesenchymal Transition of Triple-Negative Breast Cancer: Identification of Therapeutic Targets.Interdisciplinary sciences, computational life sciences · 2026Article
- HSP90 inhibition disrupts telomere maintenance and promotes chromosomal instability (CIN) in cancer cells.Research square · 2026Article
- Neutrophil elastase promotes low molecular weight cyclin E1 formation to accelerate osteosarcoma proliferation.Frontiers in immunology · 2025Article
- Overcoming cancer drug resistance through small-molecule targeting of HSP90 and HSP70.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.Journal of hematology & oncology · 2024Review
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Telomeres and telomerase in Sarcoma disease and therapy.International journal of medical sciences · 2024Review
- Article
- RNA 5-methylcytosine status is associated with DNMT2/TRDMT1 nuclear localization in osteosarcoma cell lines.Journal of bone oncology · 2022Article
- Telomerase gene therapy: a remission toward cancer.Medical oncology (Northwood, London, England) · 2022Review
- Role of HSP90α in osteoclast formation and osteoporosis development.Experimental and therapeutic medicine · 2022Article
- Selective Elimination of Osteosarcoma Cell Lines with Short Telomeres by Ataxia Telangiectasia and Rad3-Related Inhibitors.ACS pharmacology & translational science · 2020Article
- From the Clinic to the Bench and Back Again in One Dog Year: How a Cross-Species Pipeline to Identify New Treatments for Sarcoma Illuminates the Path Forward in Precision Medicine.Frontiers in oncology · 2020Article
- Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies.Genome medicine · 2016Review
- Relationship Between P15 Gene Mutation and Formation and Metastasis of Malignant Osteosarcoma.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unsatisfactory outcomes for osteosarcoma necessitate novel therapeutic strategies. This study evaluated the effect of the telomerase inhibitor imetelstat in pre-clinical models of human osteosarcoma. Because the chaperone molecule HSP90 facilitates the assembly of telomerase protein, the ability of the HSP90 inhibitor alvespimycin to potentiate the effect of the telomerase inhibitor was assessed. The effect of single or combined treatment with imetelstat and alvespimycin on long-term growth was assessed in osteosarcoma cell lines (143B, HOS and MG-63) and xenografts derived from 143B cells. Results indicated that imetelstat as a single agent inhibited telomerase activity, induced telomere shortening, and inhibited growth in all 3 osteosarcoma cell lines, though the bulk cell cultures did not undergo growth arrest. Combined treatment with imetelstat and alvespimycin resulted in diminished telomerase activity and shorter telomeres compared to either agent alone as well as higher levels of γH2AX and cleaved caspase-3, indicative of increased DNA damage and apoptosis. With dual telomerase and HSP90 inhibition, complete growth arrest of bulk cell cultures was achieved. In xenograft models, all 3 treatment groups significantly inhibited tumor growth compared with the placebo-treated control group, with the greatest effect seen in the combined treatment group (imetelstat, p = 0.045, alvespimycin, p = 0.034; combined treatment, p = 0.004). In conclusion, HSP90 inhibition enhanced the effect of telomerase inhibition in pre-clinical models of osteosarcoma. Dual targeting of telomerase and HSP90 warrants further investigation as a therapeutic strategy.
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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.