ArticleBMC cancer2014
Dexrazoxane may prevent doxorubicin-induced DNA damage via depleting both topoisomerase II isoforms.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.
- Dexrazoxane for preventing or reducing cardiotoxicity in adults and children with cancer receiving anthracyclines.The Cochrane database of systematic reviews · 2022Pooled it
- Interim Analysis of the Phase II Study: Noninferiority Study of Doxorubicin with Upfront Dexrazoxane plus Olaratumab for Advanced or Metastatic Soft-Tissue Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- HydroMg attenuates doxorubicin-induced myocardial injury via promoting mitochondrial function.Medical gas research · 2027Article
- Phosphatidylserine-based liposomes encapsulating DMX-5804 protect against doxorubicin-induced cardiotoxicity.RSC pharmaceutics · 2026Article
- Barettin Suppresses Pancreatic Ductal Adenocarcinoma Proliferation via Topoisomerase IIα Inhibition.Marine drugs · 2026Article
- Safety and Treatment Efficacy of Systemic, Locoregional, and Nanoparticle Encapsulated Anthracycline Chemotherapy: Insights Into Cardiotoxicity.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- DNA topological regulation in RNA polymerase II transcription.Cellular & molecular biology letters · 2026Review
- Phosphatidylserine-Based Liposomes Encapsulating DMX-5804 Protect Against Doxorubicin-Induced Cardiotoxicity.bioRxiv : the preprint server for biology · 2026Article
- Dexrazoxane Protects Against Hand-Foot Syndrome-Like Skin Damage in Pegylated Liposomal Doxorubicin-Treated Mice.Journal of toxicology · 2026Article
- A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy.Oncology research · 2026Review
- The multifaceted mechanisms of Tanshinone IIA in doxorubicin-induced cardiotoxicity.Frontiers in medicine · 2026Review
- Treatment of left ventricular dysfunction during cancer therapy: a comprehensive review.Drugs in context · 2026Review
- Cardiovascular and Oncologic Considerations in Adult Hodgkin Lymphoma: JACC: CardioOncology State-of the-Art Review.JACC. CardioOncology · 2025Review
- Association of early dexrazoxane with reduced cardiotoxicity risk in sarcoma patients treated with anthracycline chemotherapy.The oncologist · 2025Article
- TOP2B modulates DNA supercoiling and chromatin contacts during transcriptional induction.Science advances · 2025Article
- The Role of Diastolic Stress Echo and Myocardial Work in Early Detection of Cardiac Dysfunction in Women with Breast Cancer Undergoing Chemotherapy.Biomedicines · 2025Article
- Cardio-Oncology Considerations for Breast Cancer: Risk Stratification, Monitoring, and Treatment.Oncology (Williston Park, N.Y.) · 2025Review
- SiRNA-mediated knockdown of TOP2B protects hiPSC-derived cardiomyocytes from doxorubicin-induced toxicity.Life sciences · 2025Article
- Prevention of cancer-therapy related cardiac dysfunction.Current heart failure reports · 2025Review
- Unveiling the Complexities: Exploring Mechanisms of Anthracyclineinduced Cardiotoxicity.Current cardiology reviews · 2025Review
35 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
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe bisdioxopiperazine dexrazoxane (DRZ) prevents anthracycline-induced heart failure, but its clinical use is limited by uncertain cardioprotective mechanism and by concerns of interference with cancer response to anthracyclines and of long-term safety.
methodsWe investigated the effects of DRZ on the stability of topoisomerases IIα (TOP2A) and IIβ (TOP2B) and on the DNA damage generated by poisoning these enzymes by the anthracycline doxorubicin (DOX).
resultsDRZ given i.p. transiently depleted in mice the predominant cardiac isoform Top2b. The depletion was also seen in H9C2 cardiomyocytes and it was attenuated by mutating the bisdioxopiperazine binding site of TOP2B. Consistently, the accumulation of DOX-induced DNA double strand breaks (DSB) by wild-type, although not by mutant TOP2B, was reduced by DRZ. In contrast, the DRZ analogue ICRF-161, which is capable of iron chelation but not of TOP2B binding and cardiac protection, did not deplete TOP2B and did not prevent the accumulation of DOX-induced DSB. TOP2A, re-expressed in cultured cardiomyocytes by fresh serum, was depleted by DRZ along with TOP2B. DRZ depleted TOP2A also from fibrosarcoma-derived cells, but not from lung cancer-derived and human embryo-derived cells. DRZ-mediated TOP2A depletion reduced the accumulation of DOX-induced DSB.
conclusionsTaken together, our data support a model of anthracycline-induced heart failure caused by TOP2B-mediated DSB and of its prevention by DRZ via TOP2B degradation rather than via iron chelation. The depletion of TOP2B and TOP2A suggests an explanation for the reported DRZ interference with cancer response to anthracyclines and for DRZ side-effects.
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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.