ArticleEMBO molecular medicine2015
Therapeutic inhibition of TRF1 impairs the growth of p53-deficient K-RasG12V-induced lung cancer by induction of telomeric DNA damage.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The trial behind it
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
39 citing papers in PubMed, 54 citations in OpenAlex.
- Trial
- Targeting telomeres in brain vasculature does not impede initiation and progression of glioblastoma.PloS one · 2026Article
- Discovery of first-in-class inhibitors of the TRF1:TIN2 protein:protein interaction by fragment screening.Scientific reports · 2025Article
- Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.Experimental hematology & oncology · 2025Review
- The role of telomere and telomerase in cancer and novel therapeutic target: narrative review.Frontiers in oncology · 2025Review
- α-Terpineol Induces Shelterin Components TRF1 and TRF2 to Mitigate Senescence and Telomere Integrity Loss via A Telomerase-Independent Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- Telomere-related DNA damage response pathways in cancer therapy: prospective targets.Frontiers in pharmacology · 2024Review
- Deubiquitinases in cancer.Nature reviews. Cancer · 2023Review
- Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).Cancer cell international · 2023Review
- The Molecular Mechanisms and Therapeutic Prospects of Alternative Lengthening of Telomeres (ALT).Cancers · 2023Review
- MiR-182-3p targets TRF2 and impairs tumor growth of triple-negative breast cancer.EMBO molecular medicine · 2023Article
- Targeting telomeres: advances in telomere maintenance mechanism-specific cancer therapies.Nature reviews. Cancer · 2022Review
- Telomere Targeting Approaches in Cancer: Beyond Length Maintenance.International journal of molecular sciences · 2022Review
- Prognostic value of TERF1 expression in prostate cancer.Journal of the Egyptian National Cancer Institute · 2021Article
- Short and dysfunctional telomeres protect from allergen-induced airway inflammation.Aging cell · 2021Article
- Naked mole rat TRF1 safeguards glycolytic capacity and telomere replication under low oxygen.Science advances · 2021Article
- Dynamics of TRF1 organizing a single human telomere.Nucleic acids research · 2021Article
- Targeting telomerase for cancer therapy.Oncogene · 2020Review
- Role of Telomeres and Telomeric Proteins in Human Malignancies and Their Therapeutic Potential.Cancers · 2020Review
- Therapeutic Targets in Telomerase and Telomere Biology of Cancers.Indian journal of clinical biochemistry : IJCB · 2020Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Telomeres are considered anti-cancer targets, as telomere maintenance above a minimum length is necessary for cancer growth. Telomerase abrogation in cancer-prone mouse models, however, only decreased tumor growth after several mouse generations when telomeres reach a critically short length, and this effect was lost upon p53 mutation. Here, we address whether induction of telomere uncapping by inhibition of the TRF1 shelterin protein can effectively block cancer growth independently of telomere length. We show that genetic Trf1 ablation impairs the growth of p53-null K-Ras(G12V)-induced lung carcinomas and increases mouse survival independently of telomere length. This is accompanied by induction of telomeric DNA damage, apoptosis, decreased proliferation, and G2 arrest. Long-term whole-body Trf1 deletion in adult mice did not impact on mouse survival and viability, although some mice showed a moderately decreased cellularity in bone marrow and blood. Importantly, inhibition of TRF1 binding to telomeres by small molecules blocks the growth of already established lung carcinomas without affecting mouse survival or tissue function. Thus, induction of acute telomere uncapping emerges as a potential new therapeutic target for lung cancer.
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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.