ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
A Modified Nucleoside 6-Thio-2'-Deoxyguanosine Exhibits Antitumor Activity in Gliomas.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Brain Organoids: Emerging Platforms for Modern Neuroscience.Brain sciences · 2026Review
- SMARCAL1 is a targetable synthetic lethal therapeutic vulnerability in ATRX-deficient gliomas that use alternative lengthening of telomeres.Neuro-oncology · 2026Article
- Therapeutic 6-thio-deoxyguanosine inhibits telomere elongation in cancer cells by inducing a non-productive stalled telomerase complex.Nature communications · 2025Article
- Novel telomere-targeting dual-pharmacophore dinucleotide prodrugs for anticancer therapy.Nucleic acids research · 2025Article
- Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine.Journal of nanobiotechnology · 2025Article
- Characterizing Sensitivity to Vincristine, Irinotecan, and Telomerase-targeted Therapy in Diffuse Anaplastic Wilms Tumor Patient-derived XenograftsJournal of pediatric surgery · 2025Article
- The Regulation of Cellular Senescence in Cancer.Biomolecules · 2025Review
- Canonical and non-canonical functions of the non-coding RNA component (TERC) of telomerase complex.Cell & bioscience · 2025Review
- Broad-spectrum antitumor analysis of the telomerase activity inhibitor TPCH derived from the human constitutively expressed protein LPTS/PinX1.Frontiers in oncology · 2025Article
- Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy.Scientific reports · 2024Article
- Aging, Cancer, and Inflammation: The Telomerase Connection.International journal of molecular sciences · 2024Review
- Mechanisms of telomere maintenance and associated therapeutic vulnerabilities in malignant gliomas.Neuro-oncology · 2024Review
- Prognostic Impact ofCancers · 2024Article
- Whole tumor analysis reveals early origin of the TERT promoter mutation and intercellular heterogeneity in TERT expression.Neuro-oncology · 2024Article
- The regulations of telomerase reverse transcriptase (TERT) in cancer.Cell death & disease · 2024Review
- Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy.bioRxiv : the preprint server for biology · 2024Article
- Telomere-related DNA damage response pathways in cancer therapy: prospective targets.Frontiers in pharmacology · 2024Review
- Pooled genetic screens to identify vulnerabilities in TERT-promoter-mutant glioblastoma.Oncogene · 2023Article
- Advances in Treatment of Isocitrate Dehydrogenase (IDH)-Wildtype Glioblastomas.Current neurology and neuroscience reports · 2023Review
- Looking Beyond the Glioblastoma Mask: Is Genomics the Right Path?Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
38 authors at 11 institutions in 2 countries.
Funding
Abstract
purposeTo investigate the therapeutic role of a novel telomere-directed inhibitor, 6-thio-2'-deoxyguanosine (THIO) in gliomas both EXPERIMENTAL
designA panel of human and mouse glioma cell lines was used to test therapeutic efficacy of THIO using cell viability assays, flow cytometric analyses, and immunofluorescence. Integrated analyses of RNA sequencing and reverse-phase protein array data revealed the potential antitumor mechanisms of THIO. Four patient-derived xenografts (PDX), two patient-derived organoids (PDO), and two xenografts of human glioma cell lines were used to further investigate the therapeutic efficacy of THIO.
resultsTHIO was effective in the majority of human and mouse glioma cell lines with no obvious toxicity against normal astrocytes. THIO as a monotherapy demonstrated efficacy in three glioma cell lines that had acquired resistance to temozolomide. In addition, THIO showed efficacy in four human glioma cell lines grown as neurospheres by inducing apoptotic cell death. Mechanistically, THIO induced telomeric DNA damage not only in glioma cell lines but also in PDX tumor specimens. Integrated computational analyses of transcriptomic and proteomic data indicated that THIO significantly inhibited cell invasion, stem cell, and proliferation pathways while triggering DNA damage and apoptosis. Importantly, THIO significantly decreased tumor proliferation in two PDO models and reduced the tumor size of a glioblastoma xenograft and a PDX model.
conclusionsThe current study established the therapeutic role of THIO in primary and recurrent gliomas and revealed the acute induction of telomeric DNA damage as a primary antitumor mechanism of THIO in gliomas.
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