ArticleNature communications2024
A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Research progress on immune microenvironment and biomarkers of small cell lung cancer.Journal of thoracic disease · 2026Review
- cGAS-STING pathway in lung cancer and emerging therapeutic approaches.Drug discovery today · 2026Review
- Emerging Strategies for Antitumor Immunotherapy and Antiviral Defense Through the cGAS-STING Pathway.International journal of nanomedicine · 2026Review
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- Advancing small cell lung cancer metastasis research: innovations in preclinical mouse models.Cancer metastasis reviews · 2025Review
- Cell-selective telomere damage by thiopurine-based oligonucleotide for diffuse large B cell lymphoma immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Novel telomere-targeting dual-pharmacophore dinucleotide prodrugs for anticancer therapy.Nucleic acids research · 2025Article
- Prediction of lung adenocarcinoma prognosis and clinical treatment efficacy by telomere-associated gene risk model.Discover oncology · 2025Article
- Characterizing Sensitivity to Vincristine, Irinotecan, and Telomerase-targeted Therapy in Diffuse Anaplastic Wilms Tumor Patient-derived XenograftsJournal of pediatric surgery · 2025Article
- GSK-3484862, a DNMT1 degrader, promotesNAR cancer · 2025Article
- TERT Immunohistochemistry in Thin Melanomas Compared to Melanocytic Nevi.Diagnostics (Basel, Switzerland) · 2025Article
- Multi-Omics Integration Analysis Revealed That miR-375-3p Is a Two-Sided Factor Regulating the Development and TUMORIGENESIS of Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Current and future therapies for small cell lung carcinoma.Journal of hematology & oncology · 2025Review
- Machine learning-based identification of telomere-related gene signatures for prognosis and immunotherapy response in hepatocellular carcinoma.Molecular cytogenetics · 2025Article
- Novel and potent MICA/B antibody is therapeutically effective inJournal for immunotherapy of cancer · 2025Article
- Recent progress in human telomerase structure and its therapeutic targeting.Frontiers in molecular biosciences · 2025Review
- Molecular and Cellular Mechanisms of Immunosenescence: Modulation Through Interventions and Lifestyle Changes.Biology · 2024Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
There are few effective treatments for small cell lung cancer (SCLC) underscoring the need for innovative therapeutic approaches. This study focuses on exploiting telomerase, a critical SCLC dependency as a therapeutic target. A prominent characteristic of SCLC is their reliance on telomerase activity, a key enzyme essential for their continuous proliferation. Here we utilize a nucleoside analog, 6-Thio-2'-deoxyguanosine (6TdG) currently in phase II clinical trials, that is preferentially incorporated by telomerase into telomeres leading to telomere dysfunction. Using preclinical mouse and human derived models we find low intermittent doses of 6TdG inhibit tumor growth and reduce metastatic burden. Anti-tumor efficacy correlates with a reduction in a subpopulation of cancer initiating like cells (CICs) identified by their expression of L1CAM/CD133 and highest telomerase activity. 6TdG treatment also leads to activation of innate and adaptive anti-tumor responses. Mechanistically, 6TdG depletes CICs and induces type-I interferon signaling leading to tumor immune visibility by activating tumor cell STING signaling. We also observe increased sensitivity to irradiation after 6TdG treatment in both syngeneic and humanized SCLC xenograft models both of which are dependent on the presence of host immune cells. This study underscores the immune-enhancing and metastasis-reducing effects of 6TdG, employing a range of complementary in vitro and in vivo SCLC preclinical models providing a potential therapeutic approach to SCLC.
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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.