ArticleCellular oncology (Dordrecht, Netherlands)2022
Telomerase-targeting compounds Imetelstat and 6-thio-dG act synergistically with chemotherapy in high-risk neuroblastoma models.
Article in Cellular oncology (Dordrecht, Netherlands), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 21 citations in OpenAlex.
- Telomere damage enhances immunogenicity of neuroblastoma and accelerates response to anti-PD-L1 treatment.Oncoimmunology · 2026Article
- A lactylation-associated gene signature predicts prognosis in neuroblastoma and identifies RPS6KA6 as a candidate biomarker.BMC cancer · 2026Article
- Diagnosis and management of neuroblastoma in children.World journal of pediatric surgery · 2026Review
- Clinical Significance ofJCO precision oncology · 2025Article
- Development of a microarray based telomerase binding assay reveals unusual binding of a cytochalasin derivative.Scientific reports · 2025Article
- Characterizing Sensitivity to Vincristine, Irinotecan, and Telomerase-targeted Therapy in Diffuse Anaplastic Wilms Tumor Patient-derived XenograftsJournal of pediatric surgery · 2025Article
- TERT Immunohistochemistry in Thin Melanomas Compared to Melanocytic Nevi.Diagnostics (Basel, Switzerland) · 2025Article
- Peripheral neuroblastic tumors behaving badly: an update on high-risk morphologic and molecular groupings.Virchows Archiv : an international journal of pathology · 2025Review
- Canonical and non-canonical functions of the non-coding RNA component (TERC) of telomerase complex.Cell & bioscience · 2025Review
- Mechanisms and molecular characterization of relapsed/refractory neuroblastomas.Frontiers in oncology · 2025Review
- Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1.Frontiers in oncology · 2025Article
- Recent progress in human telomerase structure and its therapeutic targeting.Frontiers in molecular biosciences · 2025Review
- The Pivotal Role of Preclinical Animal Models in Anti-Cancer Drug Discovery and Personalized Cancer Therapy Strategies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Mechanisms of telomere maintenance and associated therapeutic vulnerabilities in malignant gliomas.Neuro-oncology · 2024Review
- The regulations of telomerase reverse transcriptase (TERT) in cancer.Cell death & disease · 2024Review
- Telomere-related DNA damage response pathways in cancer therapy: prospective targets.Frontiers in pharmacology · 2024Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe majority of high-risk neuroblastomas harbor telomerase activity, and telomerase-interacting compounds, such as 6-thio-2'-deoxyguanosine (6-thio-dG), have been found to impair the growth of telomerase-positive neuroblastoma cell lines. It has remained unclear, however, how such drugs can be combined with other compounds used in current treatment concepts for neuroblastoma patients.
methodsGrowth-inhibitory effects of varying concentrations of 6-thio-dG in combination with etoposide, doxorubicin or ceritinib were determined in eight telomerase-positive neuroblastoma cell lines with distinct genetic backgrounds. Tumor growth inhibition of subcutaneous xenografts from three different cell lines was assessed upon treatment with 6-thio-dG, the competitive telomerase inhibitor imetelstat, etoposide, or combinations of these compounds.
resultsRobust synergistic anti-tumor effects were observed for combinations of 6-thio-dG and etoposide or doxorubicin, but not for 6-thio-dG and ceritinib, in telomerase-positive neuroblastoma cell lines in vitro. Treatment of mouse xenografts with combinations of 6-thio-dG and etoposide significantly attenuated tumor growth and improved mouse survival over etoposide alone in two of three cell line models. Treatment of xenograft tumors by imetelstat monotherapy decreased telomerase activity by roughly 50% and significantly improved survival over control in all three models, whereas treatment with imetelstat plus etoposide led to enhanced survival over etoposide monotherapy in one model. Mechanistically, the synergistic effect was found to be due to both increased apoptosis and cell cycle arrest.
conclusionOur study indicates that telomerase is an actionable target in telomerase-positive neuroblastoma, and demonstrates that combination therapies including telomerase-interacting compounds may improve the efficacy of established cytotoxic drugs. Targeting telomerase may thus represent a therapeutic option in high-risk neuroblastoma patients.
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