ArticleNature communications2023
Signalling inhibition by ponatinib disrupts productive alternative lengthening of telomeres (ALT).
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Large-scale drug sensitivity, gene dependency, and proteogenomic analyses of telomere maintenance mechanisms in cancer cells.Nature communications · 2025Article
- Cancer network pharmacology: multi-network regulatory mechanisms and future directions.Medical oncology (Northwood, London, England) · 2025Review
- Review
- Targeting FANCM by antisense oligonucleotides in ALT-positive cancers.Molecular therapy. Nucleic acids · 2025Article
- Multiple functions of the ALT favorite helicase, BLM.Cell & bioscience · 2025Review
- Identification of modulators of the ALT pathway through a native FISH-based optical screen.Cell reports · 2025Article
- Article
- Prognostic and Immunological Implications of Telomere Maintenance-Related Genes in Breast Cancer: A Mechanistic Exploration.Breast cancer (Dove Medical Press) · 2025Article
- Identification of Novel Modulators of the ALT Pathway Through a Native FISH-Based Optical Screen.bioRxiv : the preprint server for biology · 2024Article
- A First-in-Class High-Throughput Screen to Discover Modulators of the Alternative Lengthening of Telomeres (ALT) Pathway.ACS pharmacology & translational science · 2024Article
- Alternative lengthening of telomeres: mechanism and the pathogenesis of cancer.Journal of clinical pathology · 2024Article
- Comparative Application of Terminal Restriction Fragment Analysis Tools to Large-Scale Genomic Assays.International journal of molecular sciences · 2023Article
- Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs.Nature communications · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Alternative lengthening of telomeres (ALT) supports telomere maintenance in 10-15% of cancers, thus representing a compelling target for therapy. By performing anti-cancer compound library screen on isogenic cell lines and using extrachromosomal telomeric C-circles, as a bona fide marker of ALT activity, we identify a receptor tyrosine kinase inhibitor ponatinib that deregulates ALT mechanisms, induces telomeric dysfunction, reduced ALT-associated telomere synthesis, and targets, in vivo, ALT-positive cells. Using RNA-sequencing and quantitative phosphoproteomic analyses, combined with C-circle level assessment, we find an ABL1-JNK-JUN signalling circuit to be inhibited by ponatinib and to have a role in suppressing telomeric C-circles. Furthermore, transcriptome and interactome analyses suggest a role of JUN in DNA damage repair. These results are corroborated by synergistic drug interactions between ponatinib and either DNA synthesis or repair inhibitors, such as triciribine. Taken together, we describe here a signalling pathway impacting ALT which can be targeted by a clinically approved drug.
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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.