ReviewJournal of cancer research and clinical oncology2017
Clinical pharmacology and clinical trials of ribonucleotide reductase inhibitors: is it a viable cancer therapy?
Review in Journal of cancer research and clinical oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Combined Inhibition of ATR and Ribonucleotide Reductase Induces Synergistic Antineoplastic Activity in Osteosarcoma Cells.Cancer reports (Hoboken, N.J.) · 2026Article
- Significance of Ribonucleoside-diphosphate Reductase Subunit M2 in Lung Adenocarcinoma.Current gene therapy · 2025Article
- New Insights into Aspirin's Anticancer Activity: The Predominant Role of Its Iron-Chelating Antioxidant Metabolites.Antioxidants (Basel, Switzerland) · 2024Review
- ORAOV1, CCND1, and MIR548K Are the Driver Oncogenes of the 11q13 Amplicon in Squamous Cell Carcinoma.Molecular cancer research : MCR · 2024Article
- Exploring the Use of Intracellular Chelation and Non-Iron Metals to Program Ferroptosis for Anticancer Application.Inorganics · 2024Article
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- Synergistic anticancer activity of combined ATR and ribonucleotide reductase inhibition in Ewing's sarcoma cells.Journal of cancer research and clinical oncology · 2023Article
- From a drug repositioning to a structure-based drug design approach to tackle acute lymphoblastic leukemia.Nature communications · 2023Article
- Deferiprone and Iron-Maltol: Forty Years since Their Discovery and Insights into Their Drug Design, Development, Clinical Use and Future Prospects.International journal of molecular sciences · 2023Review
- New Iron Metabolic Pathways and Chelation Targeting Strategies Affecting the Treatment of All Types and Stages of Cancer.International journal of molecular sciences · 2022Review
- Screening of traditional Chinese medicine monomers as ribonucleotide reductase M2 inhibitors for tumor treatment.World journal of clinical cases · 2022Article
- Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present.Biomolecules · 2022Review
- The Multifaceted Roles of Mast Cells in Immune Homeostasis, Infections and Cancers.International journal of molecular sciences · 2022Review
- Mechanistic Insights of Chelator Complexes with Essential Transition Metals: Antioxidant/Pro-Oxidant Activity and Applications in Medicine.International journal of molecular sciences · 2022Review
- Antisense Oligonucleotide-Mediated Splice Switching: Potential Therapeutic Approach for Cancer Mitigation.Cancers · 2021Review
- Nanomedicine for Immunotherapy Targeting Hematological Malignancies: Current Approaches and Perspective.Nanomaterials (Basel, Switzerland) · 2021Review
- Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models.Pharmaceutics · 2021Article
- Triapine Analogues and Their Copper(II) Complexes: Synthesis, Characterization, Solution Speciation, Redox Activity, Cytotoxicity, and mR2 RNR Inhibition.Inorganic chemistry · 2021Article
- Article
- Cancer interception by interceptor molecules: mechanistic, preclinical and human translational studies with chlorophylls.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeRibonucleotide reductase (RR) enzymes (RR1 and RR2) play an important role in the reduction of ribonucleotides to deoxyribonucleotides which is involved in DNA replication and repair. Augmented RR activity has been ascribed to uncontrolled cell growth and tumorigenic transformation.
methodsThis review mainly focuses on several biological and chemical RR inhibitors (e.g., siRNA, GTI-2040, GTI-2501, triapine, gemcitabine, and clofarabine) that have been evaluated in clinical trials with promising anticancer activity from 1960's till 2016. A summary on whether their monotherapy or combination is still effective for further use is discussed.
resultsAmong the RR2 inhibitors evaluated, GTI-2040, siRNA, gallium nitrate and didox were more efficacious as a monotherapy, whereas triapine was found to be more efficacious as combination agent. Hydroxyurea is currently used more in combination therapy, even though it is efficacious as a monotherapy. Gallium nitrate showed mixed results in combination therapy, while the combination activity of didox is yet to be evaluated. RR1 inhibitors that have long been used in chemotherapy such as gemcitabine, cladribine, fludarabine and clofarabine are currently used mostly as a combination therapy, but are equally efficacious as a monotherapy, except tezacitabine which did not progress beyond phase I trials.
conclusionsBased on the results of clinical trials, we conclude that RR inhibitors are viable treatment options, either as a monotherapy or as a combination in cancer chemotherapy. With the recent advances made in cancer biology, further development of RR inhibitors with improved efficacy and reduced toxicity is possible for treatment of variety of cancers.
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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.