ArticleCell death & disease2018
A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Pooled it
- Wnt3a-expressing cancer stem cells impair CD8Oncoimmunology · 2025Article
- PDX models for functional precision oncology and discovery science.Nature reviews. Cancer · 2025Review
- The roles of patient-derived xenograft models and artificial intelligence toward precision medicine.MedComm · 2024Review
- 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
- Targeting the DNA repair enzymes MTH1 and OGG1 as a novel approach to treat inflammatory diseases.Basic & clinical pharmacology & toxicology · 2022Review
- A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX).Journal of cancer research and clinical oncology · 2022Article
- Genetics and Therapeutic Responses to Tumor-Infiltrating Lymphocyte Therapy of Pancreatic Cancer Patient-Derived Xenograft Models.Gastro hep advances · 2022Article
- MTH1 as a target to alleviate T cell driven diseases by selective suppression of activated T cells.Cell death and differentiation · 2022Article
- Optimizing Drug Response Study Design in Patient-Derived Tumor Xenografts.Cancer informatics · 2022Article
- MTH1 Inhibitor TH1579 Induces Oxidative DNA Damage and Mitotic Arrest in Acute Myeloid Leukemia.Cancer research · 2021Article
- Intussusceptive Angiogenesis in Human Metastatic Malignant Melanoma.The American journal of pathology · 2021Article
- Karonudib has potent anti-tumor effects in preclinical models of B-cell lymphoma.Scientific reports · 2021Article
- Combining Neratinib with CDK4/6, mTOR, and MEK Inhibitors in Models of HER2-positive Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Antitumour activity of TH1579, a novel MTH1 inhibitor, against castration-resistant prostate cancer.Oncology letters · 2021Article
- BET bromodomain inhibitor HMBA synergizes with MEK inhibition in treatment of malignant glioma.Epigenetics · 2021Article
- Novel Patient Metastatic Pleural Effusion-Derived Xenograft Model of Renal Medullary Carcinoma Demonstrates Therapeutic Efficacy of Sunitinib.Frontiers in oncology · 2021Article
- AXL and CAV-1 play a role for MTH1 inhibitor TH1579 sensitivity in cutaneous malignant melanoma.Cell death and differentiation · 2020Article
- MTH1 favors mesothelioma progression and mediates paracrine rescue of bystander endothelium from oxidative damage.JCI insight · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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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.