ArticleOncogene2018
Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- 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
- Canonical and non-canonical functions of the non-coding RNA component (TERC) of telomerase complex.Cell & bioscience · 2025Review
- Selective abrogation of S6K2 identifies lipid homeostasis as a survival vulnerability in MAPK inhibitor-resistantScience translational medicine · 2025Article
- Rare Drivers at Low Prevalence with High Cancer Effects in T-Cell and B-Cell Pediatric Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Article
- IMPDH Inhibition Decreases TERT Expression and Synergizes the Cytotoxic Effect of Chemotherapeutic Agents in Glioblastoma Cells.International journal of molecular sciences · 2024Article
- The regulations of telomerase reverse transcriptase (TERT) in cancer.Cell death & disease · 2024Review
- A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer.Nature communications · 2024Article
- Article
- Review
- Melanoma: Molecular genetics, metastasis, targeted therapies, immunotherapies, and therapeutic resistance.Genes & diseases · 2022Review
- Telomere Targeting Approaches in Cancer: Beyond Length Maintenance.International journal of molecular sciences · 2022Review
- Review
- Review
- Metabolic Interplay between the Immune System and Melanoma Cells: Therapeutic Implications.Biomedicines · 2021Review
- Novel insights into the pathogenesis and treatment of NRAS mutant melanoma.Expert review of precision medicine and drug development · 2021Article
- TERT amplification but not activation of canonical Wnt/β-catenin pathway is involved in acral lentiginous melanoma progression to metastasis.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Targeting telomerase for cancer therapy.Oncogene · 2020Review
- Inhibition of NRAS Signaling in Melanoma through Direct Depalmitoylation Using Amphiphilic Nucleophiles.ACS chemical biology · 2020Article
- Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma.International journal of molecular sciences · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Targeting RAS is one of the greatest challenges in cancer therapy. Oncogenic mutations in NRAS are present in over 25% of melanomas and patients whose tumors harbor NRAS mutations have limited therapeutic options and poor prognosis. Thus far, there are no clinical agents available to effectively target NRAS or any other RAS oncogene. An alternative approach is to identify and target critical tumor vulnerabilities or non-oncogene addictions that are essential for tumor survival. We investigated the consequences of NRAS blockade in NRAS-mutant melanoma and show that decreased expression of the telomerase catalytic subunit, TERT, is a major consequence. TERT silencing or treatment of NRAS-mutant melanoma with the telomerase-dependent telomere uncapping agent, 6-thio-2'-deoxyguanosine (6-thio-dG), led to rapid cell death, along with evidence of both telomeric and non-telomeric DNA damage, increased ROS levels, and upregulation of a mitochondrial antioxidant adaptive response. Combining 6-thio-dG with the mitochondrial inhibitor Gamitrinib attenuated this adaptive response and more effectively suppressed NRAS-mutant melanoma. Our study uncovers a robust dependency of NRAS-mutant melanoma on TERT, and provides proof-of-principle for a new combination strategy to combat this class of tumors, which could be expanded to other tumor types.
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What OpenQuestion holds
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.