ArticleScientific reports2019
Differential anti-tumour effects of MTH1 inhibitors in patient-derived 3D colorectal cancer cultures.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- The MTH1 inhibitor TH287 sensitized Castration-Resistant Prostate Cancer cells to ionizing radiation therapy.International urology and nephrology · 2026Article
- Article
- 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
- Targeting the nucleic acid oxidative damage repair enzyme MTH1: a promising therapeutic option.Frontiers in cell and developmental biology · 2024Review
- Uncover DNA damage and repair-related gene signature and risk score model for glioma.Annals of medicine · 2023Article
- Inhibition of human APE1 and MTH1 DNA repair proteins by dextran-coated γ-FeNanomedicine (London, England) · 2022Article
- Role of the NUDT Enzymes in Breast Cancer.International journal of molecular sciences · 2021Review
- Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives.Acta pharmaceutica Sinica. B · 2020Review
- MTH1 favors mesothelioma progression and mediates paracrine rescue of bystander endothelium from oxidative damage.JCI insight · 2020Article
- Inhibitors of DNA Glycosylases as Prospective Drugs.International journal of molecular sciences · 2020Review
- Article
- TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model.EBioMedicine · 2020Article
- 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
- The MTH1 inhibitor TH588 is a microtubule-modulating agent that eliminates cancer cells by activating the mitotic surveillance pathway.Scientific reports · 2019Article
- Mechanisms of MTH1 inhibition-induced DNA strand breaks: The slippery slope from the oxidized nucleotide pool to genotoxic damage.DNA repair · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reactive oxygen species (ROS) function as second messengers in signal transduction, but high ROS levels can also cause cell death. MTH1 dephosphorylates oxidized nucleotides, thereby preventing their incorporation into DNA and protecting tumour cells from oxidative DNA damage. Inhibitors of MTH1 (TH588 and (S)-crizotinib) were shown to reduce cancer cell viability. However, the MTH1-dependency of the anti-cancer effects of these drugs has recently been questioned. Here, we have assessed anti-tumour effects of TH588 and (S)-crizotinib in patient-derived 3D colorectal cancer cultures. Hypoxia and reoxygenation - conditions that increase intracellular ROS levels - increased sensitivity to (S)-crizotinib, but not to TH588. (S)-crizotinib reduced tyrosine phosphorylation of c-MET and ErbB3 whereas TH588 induced a mitotic cell cycle arrest, which was not affected by adding ROS-modulating compounds. Furthermore, we show that both compounds induced DNA damage that could not be prevented by adding the ROS inhibitor N-acetyl-L-cysteine. Moreover, adding ROS-modulating compounds did not alter the reduction in viability in response to TH588 and (S)-crizotinib. We conclude that TH588 and (S)-crizotinib have very clear and distinct anti-tumour effects in 3D colorectal cancer cultures, but that these effects most likely occur through distinct and ROS-independent mechanisms.
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