ArticleDNA repair2019
Increased MTH1-specific 8-oxodGTPase activity is a hallmark of cancer in colon, lung and pancreatic tissue.
Article in DNA repair, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Repurposing resveratrol for redox-mediated inhibition of MTH1 in breast cancer.Scientific reports · 2025Article
- Clinical Significance of NUDT1 (MTH1) Across Cancer Types.International journal of molecular sciences · 2025Review
- An Oxidative Stress Nano-Amplifier for Improved Tumor Elimination and Combined Immunotherapy.Advanced healthcare materials · 2024Article
- Role of MTH1 in oxidative stress and therapeutic targeting of cancer.Redox biology · 2024Review
- Article
- Targeting MutT Homolog 1 (MTH1) for Breast Cancer Suppression by Using a Novel MTH1 Inhibitor MA-24 with Tumor-Selective Toxicity.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Targeting the nucleic acid oxidative damage repair enzyme MTH1: a promising therapeutic option.Frontiers in cell and developmental biology · 2024Review
- Mitotic MTH1 Inhibitors in Treatment of Cancer.Cancer treatment and research · 2023Article
- Chemical Tools for the Study of DNA Repair.Accounts of chemical research · 2022Article
- Review
- Targeting the DNA damage response and repair in cancer through nucleotide metabolism.Molecular oncology · 2022Review
- MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia.Cancer research · 2021Article
- Article
- Biomarkers of nucleic acid oxidation - A summary state-of-the-art.Redox biology · 2021Article
- In Silico Identification of Small Molecules as New Cdc25 Inhibitors through the Correlation between Chemosensitivity and Protein Expression Pattern.International journal of molecular sciences · 2021Article
- Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives.Acta pharmaceutica Sinica. B · 2020Review
- Article
- 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
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Cellular homeostasis is dependent on a balance between DNA damage and DNA repair mechanisms. Cells are constantly assaulted by both exogenous and endogenous stimuli leading to high levels of reactive oxygen species (ROS) that cause oxidation of the nucleotide dGTP to 8-oxodGTP. If this base is incorporated into DNA and goes unrepaired, it can result in G > T transversions, leading to genomic DNA damage. MutT Homolog 1 (MTH1) is a nucleoside diphosphate X (Nudix) pyrophosphatase that can remove 8-oxodGTP from the nucleotide pool before it is incorporated into DNA by hydrolyzing it into 8-oxodGMP. MTH1 expression has been shown to be elevated in many cancer cells and is thought to be a survival mechanism by which a cancer cell can stave off the effects of high ROS that can result in cell senescence or death. It has recently become a target of interest in cancer because it is thought that inhibiting MTH1 can increase genotoxic damage and cytotoxicity. Determining the role of MTH1 in normal and cancer cells is confounded by an inability to reliably and directly measure its native enzymatic activity. We have used the chimeric ATP-releasing guanine-oxidized (ARGO) probe that combines 8-oxodGTP and ATP to measure MTH1 enzymatic activity in colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) along with patient-matched normal tissue. MTH1 8-oxodGTPase activity is significantly increased in tumors across all three tissue types, indicating that MTH1 is a marker of cancer. MTH1 activity measured by ARGO assay was compared to mRNA and protein expression measured by RT-qPCR and Western blot in the CRC tissue pairs, revealing a positive correlation between ARGO assay and Western blot, but little correlation with RT-qPCR in these samples. The adoption of the ARGO assay will help in establishing the level of MTH1 activity in model systems and in assessing the effects of MTH1 modulation in the treatment of cancer.
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