ArticleOncotarget2015
Transient rRNA synthesis inhibition with CX-5461 is sufficient to elicit growth arrest and cell death in acute lymphoblastic leukemia cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
22 citing papers in PubMed, 30 citations in OpenAlex.
- CX-5461 and doxorubicin activate a shared DNA damage-associated transcriptional response in human cardiomyocytes.G3 (Bethesda, Md.) · 2026Article
- The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment.Journal of translational medicine · 2025Review
- The Interplay Between theInternational journal of molecular sciences · 2024Review
- NAT10 resolves harmful nucleolar R-loops depending on its helicase domain and acetylation of DDX21.Cell communication and signaling : CCS · 2024Article
- Article
- Article
- The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma.Nature communications · 2021Article
- Quinacrine Induces Nucleolar Stress in Treatment-Refractory Ovarian Cancer Cell Lines.Cancers · 2021Article
- Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy.Signal transduction and targeted therapy · 2021Review
- Targeting cancer via ribosome biogenesis: the cachexia perspective.Cellular and molecular life sciences : CMLS · 2021Review
- Review
- Article
- Ubiquitin-mediated DNA damage response is synthetic lethal with G-quadruplex stabilizer CX-5461.Scientific reports · 2021Article
- Review
- Article
- The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer.International journal of molecular sciences · 2017Review
- Early nucleolar disorganization in Dictyostelium cell death.Cell death & disease · 2017Article
- Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways.PloS one · 2017Article
- Mammary epithelial morphogenesis and early breast cancer. Evidence of involvement of basal components of the RNA Polymerase I transcription machinery.Cell cycle (Georgetown, Tex.) · 2016Article
- Inhibition of RNA polymerase I transcription initiation by CX-5461 activates non-canonical ATM/ATR signaling.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enhanced rRNA synthesis is a downstream effect of many of the signaling pathways that are aberrantly activated in cancer, such as the PI3K/mTOR and MAP kinase pathways. Recently, two new rRNA synthesis inhibitors have demonstrated therapeutic effects on cancer cells while sparing normal cells. One of them, CX-5461, is currently in phase 1 clinical trials for hematological malignancies. Here, we investigate the effectiveness of transient treatment with this drug on acute lymphoblastic leukemia cells. Our results show that short exposure to CX-5461 followed by drug washout is sufficient to induce persistent G2 cell-cycle arrest and irreversible commitment to cell death, in spite of rRNA synthesis returning to normal within 24 hours of drug washout. The magnitude of cell death after transient exposure is similar to continuous exposure, but the time to cell death is relatively delayed with transient exposure. In this report, we also investigate rational drug combinations that can potentiate the effect of continuous CX-5461 treatment. We show that the checkpoint abrogator UCN-01 can relieve CX-5461-induced G2 arrest and potentiate the cytotoxic effects of CX-5461. Finally, we show that ERK1/2 is activated upon CX-5461 treatment, and that pharmacological inhibition of MEK1/2 leads to enhanced cell death in combination with CX-5461. In summary, our results provide evidence for the effectiveness of CX-5461 pulse treatment, which may minimize drug related toxicity, and evidence for enhanced effectiveness of CX-5461 in combination with other targeted agents.
Indexed as
Identifiers
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.