ReviewInvestigational new drugs2017
Metabolic carbonyl reduction of anthracyclines - role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents.
Review in Investigational new drugs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Meta analysis of bioactive compounds, miRNA, siRNA and cell death regulators as sensitizers to doxorubicin induced chemoresistance.Apoptosis : an international journal on programmed cell death · 2022Pooled it
- Review
- Nanoscale strategies: doxorubicin resistance challenges and enhancing cancer therapy with advanced nanotechnological approaches.Drug delivery and translational research · 2025Review
- Influence of Polymorphisms in Pharmacokinetics-Related Genes on the Areas Under the Plasma Concentration-Time Curves of Doxorubicin and Doxorubicinol in Patients with Diffuse Large B-Cell Lymphoma Receiving CHOP Therapy.European journal of drug metabolism and pharmacokinetics · 2025Article
- Oxyresveratrol in Breast Cancer Cells: Synergistic Effect with Chemotherapeutics Doxorubicin or Melphalan on Proliferation, Cell Cycle Arrest, and Cell Death.Pharmaceutics · 2024Article
- Article
- Idarubicin versus epirubicin in drug-eluting beads-transarterial chemoembolization for treating hepatocellular carcinoma: A real-world retrospective study.Investigational new drugs · 2023Article
- In Silico and In Vitro Assessment of Carbonyl Reductase 1 Inhibition Using ASP9521-A Potent Aldo-Keto Reductase 1C3 Inhibitor with the Potential to Support Anticancer Therapy Using Anthracycline Antibiotics.Molecules (Basel, Switzerland) · 2023Article
- Isocitrate dehydrogenase 2 inhibitor enasidenib synergizes daunorubicin cytotoxicity by targeting aldo-keto reductase 1C3 and ATP-binding cassette transporters.Archives of toxicology · 2022Article
- Structural derivatization strategies of natural phenols by semi-synthesis and total-synthesis.Natural products and bioprospecting · 2022Review
- Genetics of Anthracycline-Associated Cardiotoxicity.Frontiers in cardiovascular medicine · 2022Review
- FSCN1 acts as a promising therapeutic target in the blockade of tumor cell motility: a review of its function, mechanism, and clinical significance.Journal of Cancer · 2022Review
- Inter-Individual Variation and Cardioprotection in Anthracycline-Induced Heart Failure.Journal of clinical medicine · 2021Review
- The genetic underpinnings of anthracycline-induced cardiomyopathy predisposition.Clinical genetics · 2021Review
- Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3.Cancers · 2020Article
- Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors.Computational biology and chemistry · 2020Article
- Targeting Pharmacokinetic Drug Resistance in Acute Myeloid Leukemia Cells with CDK4/6 Inhibitors.Cancers · 2020Article
- Quinalizarin induces ROS‑mediated apoptosis via the MAPK, STAT3 and NF‑κB signaling pathways in human breast cancer cells.Molecular medicine reports · 2019Article
- Insights into the transcriptional regulation of the anthracycline reductase AKR7A2 in human cardiomyocytes.Toxicology letters · 2019Article
- Decreased Disposition of Anticancer Drugs Predominantly Eliminated via the Liver in Patients with Renal Failure.Current drug metabolism · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anthracycline antibiotics (ANT), such as doxorubicin or daunorubicin, are a class of anticancer drugs that are widely used in oncology. Although highly effective in cancer therapy, their usefulness is greatly limited by their cardiotoxicity. Possible mechanisms of ANT cardiotoxicity include their conversion to secondary alcohol metabolites (i.e. doxorubicinol, daunorubicinol) catalyzed by carbonyl reductases (CBR) and aldo-keto reductases (AKR). These metabolites are suspected to be more cardiotoxic than their parent compounds. Moreover, overexpression of ANT-reducing enzymes (CBR and AKR) are found in many ANT-resistant cancers. The secondary metabolites show decreased cytotoxic properties and are more susceptible to ABC-mediated efflux than their parent compounds; thus, metabolite formation is considered one of the mechanisms of cancer resistance. Inhibitors of CBR and AKR were found to reduce the cardiotoxicity of ANT and the resistance of cancer cells, and therefore are being investigated as prospective cardioprotective and chemosensitizing drug candidates. In this review, the significance of a two-electron reduction of ANT, including daunorubicin, epirubicin, idarubicin, valrubicin, amrubicin, aclarubicin, and especially doxorubicin, is described with respect to toxicity and efficacy of therapy. Additionally, CBR and AKR inhibitors, including monoHER, curcumin, (-)-epigallocatechin gallate, resveratrol, berberine or pixantrone, and their modulating effect on the activity of ANT is characterized and discussed as potential mechanism of action for novel therapeutics in cancer treatment.
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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.