ReviewDNA repair2019
Mechanisms of MTH1 inhibition-induced DNA strand breaks: The slippery slope from the oxidized nucleotide pool to genotoxic damage.
Review in DNA repair, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 30 citations in OpenAlex.
- Processing of DNA single-strand breaks with oxidatively damaged ends by LIG1.Nucleic acids research · 2025Article
- In vitro effect of hCG on cryptorchid patients' gubernacular cells: a predictive model for adjuvant personalized therapy.Cell communication and signaling : CCS · 2025Article
- Role of MTH1 in oxidative stress and therapeutic targeting of cancer.Redox biology · 2024Review
- Chromosome 8p engineering reveals increased metastatic potential targetable by patient-specific synthetic lethality in liver cancer.Science advances · 2023Article
- Research progress and application of the CRISPR/Cas9 gene-editing technology based on hepatocellular carcinoma.Asian journal of pharmaceutical sciences · 2023Review
- Nucleic acid adductomics - The next generation of adductomics towards assessing environmental health risks.The Science of the total environment · 2023Article
- Review
- DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients.Journal of inflammation research · 2022Article
- Identification of the Signature Genes and Network of Reactive Oxygen Species Related Genes and DNA Repair Genes in Lung Adenocarcinoma.Frontiers in medicine · 2022Article
- ROS-Induced DCTPP1 Upregulation Contributes to Cisplatin Resistance in Ovarian Cancer.Frontiers in molecular biosciences · 2022Article
- Roles for the 8-Oxoguanine DNA Repair System in Protecting Telomeres From Oxidative Stress.Frontiers in cell and developmental biology · 2021Review
- Mechanisms of telomerase inhibition by oxidized and therapeutic dNTPs.Nature communications · 2020Article
- Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients.International journal of molecular sciences · 2020Review
- The Existence of MTH1-independent 8-oxodGTPase Activity in Cancer Cells as a Compensatory Mechanism against On-target Effects of MTH1 Inhibitors.Molecular cancer therapeutics · 2020Article
- Increased MTH1-specific 8-oxodGTPase activity is a hallmark of cancer in colon, lung and pancreatic tissue.DNA repair · 2019Article
- Purine-Metabolising Enzymes and Apoptosis in Cancer.Cancers · 2019Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Unlike normal tissues, tumor cells possess a propensity for genomic instability, resulting from elevated oxidant levels produced by oncogenic signaling and aberrant cellular metabolism. Thus, targeting mechanisms that protect cancer cells from the tumor-inhibitory consequences of their redox imbalance and spontaneous DNA-damaging events is expected to have broad-spectrum efficacy and a high therapeutic index. One critical mechanism for tumor cell protection from oxidant stress is the hydrolysis of oxidized nucleotides. Human MutT homolog 1 (MTH1), the mammalian nudix (nucleoside diphosphate X) pyrophosphatase (NUDT1), protects tumor cells from oxidative stress-induced genomic DNA damage by cleansing the nucleotide pool of oxidized purine nucleotides. Depletion or pharmacologic inhibition of MTH1 results in genomic DNA strand breaks in many cancer cells. However, the mechanisms underlying how oxidized nucleotides, thought mainly to be mutagenic rather than genotoxic, induce DNA strand breaks are largely unknown. Given the recent therapeutic interest in targeting MTH1, a better understanding of such mechanisms is crucial to its successful translation into the clinic and in identifying the molecular contexts under which its inhibition is likely to be beneficial. Here we provide a comprehensive perspective on MTH1 function and its importance in protecting genome integrity, in the context of tumor-associated oxidative stress and the mechanisms that likely lead to irreparable DNA strand breaks as a result of MTH1 inhibition.
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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.