ArticleNature communications2020
CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 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
105 citing papers in PubMed, 216 citations in OpenAlex.
- JP-1302 inhibits RNA polymerase I transcription and induces nucleolar stress in cancer cell lines.Cell death discovery · 2026Article
- RAD54L coordinates the nucleolar DNA damage response to maintain rDNA stability.The EMBO journal · 2026Article
- G-quadruplex DNA reprograms the photochemistry of CX-5461 toward radical-driven anticancer activity.Nucleic acids research · 2026Article
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Structural insights into the binding of CX-5461 and MTR-106 to G-quadruplex DNA.Nucleic acids research · 2026Article
- Multi-omics dissection of R-loop dynamics in tumorigenesis: From transcription-replication conflict to therapeutic targets.Molecular therapy. Oncology · 2026Review
- [Advances in ribosome biogenesis and targeted therapies for diffuse large B-cell lymphomas].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- DNA damaging properties of G-quadruplex ligand QN-302 are potentiated by the DNA repair inhibitor Olaparib and mitigated by the molecular helicase PhpC.Genome biology · 2026Article
- CX-5461 and doxorubicin activate a shared DNA damage-associated transcriptional response in human cardiomyocytes.G3 (Bethesda, Md.) · 2026Article
- Molecular analysis of tumor recurrence using established cancer stem cell-line and drug discovery.International journal of clinical oncology · 2026Review
- Ribosome biogenesis is increased in hepatocellular carcinoma and represents a potential therapeutic target.NAR cancer · 2026Article
- Exploring RNA G-quadruplex in the rabies virus genome and its potential against RABV infection.Chemical science · 2026Article
- Fibrillarin: bridging ribosome biogenesis and apoptosis in cellular stress and disease.Apoptosis : an international journal on programmed cell death · 2026Review
- TFEB confers resistance against the chemotherapeutic agent CX-5461.Autophagy reports · 2026Article
- Targeting RNA polymerase I to boost natural killer cell anticancer activity in multiple myeloma.Cell death & disease · 2025Article
- Dual RNA Polymerase I Inhibition with CX-5461 and BMH-21 Synergizes in Breast Cancer by Activating p53-Dependent Stress.bioRxiv : the preprint server for biology · 2025Article
- C8orf33 dictates DNA double-strand break repair choice by modulating KAT8-mediated H4K16 acetylation.Cell death & disease · 2025Article
- Article
- Establishment of an imaging-based screening pipeline for the identification of human ribosome biogenesis inhibitors.BMC biology · 2025Article
- NSH76: a selective inhibitor of RRN3 and RNA polymerase I transcription with potential for cancer therapy.Journal of translational medicine · 2025Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acquired resistance to PARP inhibitors (PARPi) is a major challenge for the clinical management of high grade serous ovarian cancer (HGSOC). Here, we demonstrate CX-5461, the first-in-class inhibitor of RNA polymerase I transcription of ribosomal RNA genes (rDNA), induces replication stress and activates the DNA damage response. CX-5461 co-operates with PARPi in exacerbating replication stress and enhances therapeutic efficacy against homologous recombination (HR) DNA repair-deficient HGSOC-patient-derived xenograft (PDX) in vivo. We demonstrate CX-5461 has a different sensitivity spectrum to PARPi involving MRE11-dependent degradation of replication forks. Importantly, CX-5461 exhibits in vivo single agent efficacy in a HGSOC-PDX with reduced sensitivity to PARPi by overcoming replication fork protection. Further, we identify CX-5461-sensitivity gene expression signatures in primary and relapsed HGSOC. We propose CX-5461 is a promising therapy in combination with PARPi in HR-deficient HGSOC and also as a single agent for the treatment of relapsed disease.
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.