ArticleNeuro-oncology2025
G-quadruplex stabilizer CX-5461 effectively combines with radiotherapy to target α-thalassemia/mental retardation X-linked-deficient malignant glioma.
Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 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
8 citing papers in PubMed.
- ATRX inactivation disrupts global chromatin state and topology to dysregulate neurodevelopmental pathways in glioma pathogenesis.Nucleic acids research · 2026Article
- G-quadruplex stabilization via small molecules as a potential anti-cancer strategy.Cellular & molecular biology letters · 2026Review
- ATRX cooperates with TOP2B for replication fork stability and DNA damage response through G-quadruplex regulation.Nucleic acids research · 2025Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- Review
- G-Quadruplexes in Tumor Immune Regulation: Molecular Mechanisms and Therapeutic Prospects in Gastrointestinal Cancers.Biomedicines · 2025Review
- The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment.Journal of translational medicine · 2025Review
- Optimizing GBM organoid construction with hydrogel-based models: GelMA-HAMA scaffold supports GBM organoids with clonal growth for drug screening.Cell transplantationArticle
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
Abstract
backgroundInactivation of α-thalassemia/mental retardation X-linked (ATRX) represents a defining molecular feature in large subsets of malignant glioma. ATRX deficiency gives rise to abnormal G-quadruplex (G4) DNA secondary structures, enhancing replication stress and genomic instability. Building on earlier work, we evaluated the extent to which pharmacological G4 stabilization selectively enhances DNA damage and cell death in ATRX-deficient preclinical glioma models.
methodsUsing the G4 stabilizer CX-5461, we treated patient-derived glioma stem cells (GSCs) in vitro and GSC flank and intracranial murine xenografts in vivo to evaluate efficacy as both a single agent and in combination with ionizing radiation (IR), the latter a central element of current treatment standards.
resultsCX-5461 promoted dose-sensitive lethality in ATRX-deficient GSCs relative to ATRX-intact controls. Mechanistic studies revealed that CX-5461 disrupted histone variant H3.3 deposition, enhanced replication stress and DNA damage, activated p53-independent apoptosis, and induced G2/M arrest to a greater extent in ATRX-deficient GSCs than in ATRX-intact counterparts. These data were corroborated in vivo, where CX-5461/IR treatment profoundly delayed tumor growth and prolonged survival in mice bearing ATRX-deficient flank xenografts. Histopathological analyses revealed decreased proliferation, increased apoptosis, and significant G4 induction, replication stress, and DNA damage in CX-5461-treated tumors, both alone and in combination with IR. Finally, despite suboptimal blood-brain-barrier penetration, systemic CX-5461 treatment induced tangible pharmacodynamic effects in ATRX-deficient intracranial GSC models.
conclusionsIn totality, our work substantively demonstrates efficacy and defines mechanisms of action for G4 stabilization as a novel therapeutic strategy targeting ATRX-deficient malignant glioma, laying the groundwork for clinical translation.
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