ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Neural tumor-initiating cells have distinct telomere maintenance and can be safely targeted for telomerase inhibition.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 53 citations in OpenAlex.
- A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2015Trial
- The Role of Glia Telomere Dysfunction in the Pathogenesis of Central Nervous System Diseases.Molecular neurobiology · 2024Review
- Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting.World journal of stem cells · 2021Review
- Cancer stem cells in neuroblastoma therapy resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Article
- Application of Nanotechnology in Targeting of Cancer Stem Cells: A Review.International journal of stem cells · 2019Review
- Cancer Stem Cells in Neuroblastoma: Expanding the Therapeutic Frontier.Frontiers in molecular neuroscience · 2019Review
- Disruption of the β1L Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner.Cancer cell · 2018Article
- Bladder Cancer Stem-Like Cells: Their Origin and Therapeutic Perspectives.International journal of molecular sciences · 2015Review
- Telomerase inhibition improves tumor response to radiotherapy in a murine orthotopic model of human glioblastoma.Molecular cancer · 2015Article
- The telomerase inhibitor imetelstat alone, and in combination with trastuzumab, decreases the cancer stem cell population and self-renewal of HER2+ breast cancer cells.Breast cancer research and treatment · 2015Article
- WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.Acta neuropathologica communications · 2014Article
- Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells.Acta neuropathologica · 2014Article
- Cancer stem cells: biological functions and therapeutically targeting.International journal of molecular sciences · 2014Review
- Article
- Multidrug resistance and cancer stem cells in neuroblastoma and hepatoblastoma.International journal of molecular sciences · 2013Review
- Inhibition of BET bromodomain targets genetically diverse glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Is telomerase a viable target in cancer?Mutation research · 2012Review
- The hTERT promoter enhances the antitumor activity of an oncolytic adenovirus under a hypoxic microenvironment.PloS one · 2012Article
- The combined use of known antiviral reverse transcriptase inhibitors AZT and DDI induce anticancer effects at low concentrations.Neoplasia (New York, N.Y.) · 2012Article
- Potential clinical role of telomere length in human glioblastoma.Translational medicine @ UniSa · 2011Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeCancer recurrence is one of the major setbacks in oncology. Maintaining telomeres is essential for sustaining the limitless replicative potential of such cancers. Because telomerase is thought to be active in all tumor cells and normal stem cells, telomerase inhibition may be nonspecific and have detrimental effects on tissue maintenance and development by affecting normal stem cell self-renewal.
methodsWe examined telomerase activity, telomere maintenance, and stem cell maturation in tumor subpopulations from freshly resected gliomas, long-term, primary, neural tumor-initiating cells (TIC) and corresponding normal stem cell lines. We then tested the efficacy of the telomerase inhibitor Imetelstat on propagation and self-renewal capacity of TIC and normal stem cells in vitro and in vivo.
resultsTelomerase was undetectable in the majority of tumor cells and specific to the TIC subpopulation that possessed critically short telomeres. In contrast, normal tissue stem cells had longer telomeres and undetectable telomerase activity and were insensitive to telomerase inhibition, which results in proliferation arrest, cell maturation, and DNA damage in neural TIC. Significant survival benefit and late tumor growth arrest of neuroblastoma TIC were observed in a xenograft model (P = 0.02). Furthermore, neural TIC exhibited irreversible loss of self-renewal and stem cell capabilities even after cessation of treatment in vitro and in vivo.
conclusionsTIC exhaustion with telomerase inhibition and lack of telomerase dependency in normal stem cells add new dimensions to the telomere hypothesis and suggest that targeting TIC with telomerase inhibitors may represent a specific and safe therapeutic approach for tumors of neural origin.
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