ArticleEBioMedicine2020
TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- The MTH1 inhibitor TH287 sensitized Castration-Resistant Prostate Cancer cells to ionizing radiation therapy.International urology and nephrology · 2026Article
- NUDT1 drives osteosarcoma progression and serves as a robust predictor of clinical outcomes.Cancer cell international · 2026Article
- Mouse Models of Osteosarcoma: Unraveling Disease Mechanisms and Accelerating Drug Discovery and Development.Cancer reports (Hoboken, N.J.) · 2025Review
- Combination of cycling hyperthermia and echinacoside creates a synergistic curing effect on pancreatic cancer PANC-1 cells.Annals of medicine and surgery (2012) · 2025Article
- Repurposing resveratrol for redox-mediated inhibition of MTH1 in breast cancer.Scientific reports · 2025Article
- Exosomal LncRNA SCAMP1-AS1 enhances osteosarcoma malignancy by regulating the LKB1-AMPK signaling pathway.Scientific reports · 2025Article
- Single-Cell RNA Sequencing Reveals the Critical Role of SEC16B in Lung Metastasis of Osteosarcoma.FASEB bioAdvances · 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
- USP9X regulates the proliferation, survival, migration and invasion of gastric cancer cells by stabilizing MTH1.BMC gastroenterology · 2024Article
- 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
- Chromosome 8p engineering reveals increased metastatic potential targetable by patient-specific synthetic lethality in liver cancer.Science advances · 2023Article
- Single-cell and bulk RNA sequencing reveals Anoikis related genes to guide prognosis and immunotherapy in osteosarcoma.Scientific reports · 2023Article
- Mitotic MTH1 Inhibitors in Treatment of Cancer.Cancer treatment and research · 2023Article
- OGG1 competitive inhibitors show important off-target effects by directly inhibiting efflux pumps and disturbing mitotic progression.Frontiers in cell and developmental biology · 2023Article
- Review
- Targeting the DNA damage response and repair in cancer through nucleotide metabolism.Molecular oncology · 2022Review
- Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsteosarcoma (OS) is the most common primary malignant bone tumour. Unfortunately, no new treatments are approved and over the last 30 years the survival rate remains only 30% at 5 years for poor responders justifying an urgent need of new therapies. The Mutt homolog 1 (MTH1) enzyme prevents incorporation of oxidized nucleotides into DNA and recently developed MTH1 inhibitors may offer therapeutic potential as MTH1 is overexpressed in various cancers.
methodsThe aim of this study was to evaluate the therapeutic benefits of targeting MTH1 with two chemical inhibitors, TH588 and TH1579 on human osteosarcoma cells. Preclinical efficacy of TH1579 was assessed in human osteosarcoma xenograft model on tumour growth and development of pulmonary metastases.
findingsMTH1 is overexpressed in OS patients and tumour cell lines, compared to mesenchymal stem cells. In vitro, chemical inhibition of MTH1 by TH588 and TH1579 decreases OS cells viability, impairs their cell cycle and increases apoptosis in OS cells. TH1579 was confirmed to bind MTH1 by CETSA in OS model. Moreover, 90 mg/kg of TH1579 reduces in vivo tumour growth by 80.5% compared to non-treated group at day 48. This result was associated with the increase in 8-oxo-dG integration into tumour cells DNA and the increase of apoptosis. Additionally, TH1579 also reduces the number of pulmonary metastases.
interpretationAll these results strongly provide a pre-clinical proof-of-principle that TH1579 could be a therapeutic option for patients with osteosarcoma.
fundingThis study was supported by La Ligue Contre le Cancer, la SFCE and Enfants Cancers Santé.
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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.