ArticleBritish journal of cancer2021
The RNA polymerase I transcription inhibitor CX-5461 cooperates with topoisomerase 1 inhibition by enhancing the DNA damage response in homologous recombination-proficient high-grade serous ovarian cancer.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Novel RNA polymerase I and cyclin-dependent kinase combination therapy for the treatment of aggressive acute myeloid leukemia.Leukemia · 2026Article
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- RNA polymerase I inhibitor CX-5461 suppresses cervical cancer cell growth by inducing DNA damage and mitotic catastrophe and enhances cisplatin sensitivity.Biochemical pharmacology · 2026Article
- CX-5461 and doxorubicin activate a shared DNA damage-associated transcriptional response in human cardiomyocytes.G3 (Bethesda, Md.) · 2026Article
- Targeting RNA polymerase I to boost natural killer cell anticancer activity in multiple myeloma.Cell death & disease · 2025Article
- Exploiting dysregulated iron homeostasis to eradicate persistent high-grade serous ovarian cancer.Cell death discovery · 2025Article
- Ribosome biogenesis: A central player in liver diseases.Genes & diseases · 2025Review
- Review
- The G-quadruplex ligand CX-5461: an innovative candidate for disease treatment.Journal of translational medicine · 2025Review
- Article
- Targeting EMT using low-dose Teniposide by downregulating ZEB2-driven activation of RNA polymerase I in breast cancer.Cell death & disease · 2024Article
- Targeting the ribosome to treat multiple myeloma.Molecular therapy. Oncology · 2024Article
- CX‑5461 potentiates imatinib‑induced apoptosis in K562 cells by stimulatingExperimental and therapeutic medicine · 2024Article
- Effects of the G-quadruplex-binding drugs quarfloxin and CX-5461 on the malaria parasite Plasmodium falciparum.International journal for parasitology. Drugs and drug resistance · 2023Article
- The roles of FXYD family members in ovarian cancer: an integrated analysis by mining TCGA and GEO databases and functional validations.Journal of cancer research and clinical oncology · 2023Article
- Article
- Effect of ALA-PDT on inhibition of oral precancerous cell growth and its related mechanisms.Lasers in medical science · 2022Article
- Review
- Molecular mechanisms of platinum‑based chemotherapy resistance in ovarian cancer (Review).Oncology reports · 2022Review
- The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma.Nature communications · 2021Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntrinsic and acquired drug resistance represent fundamental barriers to the cure of high-grade serous ovarian carcinoma (HGSC), the most common histological subtype accounting for the majority of ovarian cancer deaths. Defects in homologous recombination (HR) DNA repair are key determinants of sensitivity to chemotherapy and poly-ADP ribose polymerase inhibitors. Restoration of HR is a common mechanism of acquired resistance that results in patient mortality, highlighting the need to identify new therapies targeting HR-proficient disease. We have shown promise for CX-5461, a cancer therapeutic in early phase clinical trials, in treating HR-deficient HGSC.
methodsHerein, we screen the whole protein-coding genome to identify potential targets whose depletion cooperates with CX-5461 in HR-proficient HGSC.
resultsWe demonstrate robust proliferation inhibition in cells depleted of DNA topoisomerase 1 (TOP1). Combining the clinically used TOP1 inhibitor topotecan with CX-5461 potentiates a G2/M cell cycle checkpoint arrest in multiple HR-proficient HGSC cell lines. The combination enhances a nucleolar DNA damage response and global replication stress without increasing DNA strand breakage, significantly reducing clonogenic survival and tumour growth in vivo.
conclusionsOur findings highlight the possibility of exploiting TOP1 inhibition to be combined with CX-5461 as a non-genotoxic approach in targeting HR-proficient HGSC.
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