[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-365824-105":59,"doc-detail-365824-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","clinical-significance-of-nudt1-mth1-across-cancer-types-review","Clinical Significance of NUDT1 (MTH1) Across Cancer Types - review","","MTH1 (MutT Homolog 1) is a protective enzyme that limits mutagenesis by removing oxidized free nucleotides and preventing their incorporation into DNA. Its dysfunction can elevate mutations, which explains sustained research interest in tumor cells. Many studies report MTH1 is often overexpressed rather than downregulated, supporting adaptation to increased oxidative stress from metabolic reprogramming. This review consolidates clinical evidence on MTH1 mRNA, protein, and activity across cancer types, highlighting cancers such as hepatocellular carcinoma, renal cell carcinoma, and non-small-cell lung adenocarcinoma.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/clinical-significance-of-nudt1-mth1-across-cancer-types-review/365824/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/clinical-significance-of-nudt1-mth1-across-cancer-types-review/365824.png","ImageObject",300,407,{"name":92,"@type":93},"Quinn Holloway","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is MTH1 (NUDT1) and what does it protect against?","Question",{"text":112,"@type":113},"MTH1 is an enzyme that sanitizes the free nucleotide pool by preventing oxidized dNTPs from being incorporated into DNA, reducing the risk of mutations during replication.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is MTH1 important in cancer research?",{"text":117,"@type":113},"Cancer cells often show increased oxidative stress due to metabolic reprogramming, and MTH1 is frequently overexpressed, suggesting it supports survival and uncontrolled proliferation.",{"name":119,"@type":110,"acceptedAnswer":120},"Which cancers are highlighted as showing important MTH1 involvement?",{"text":121,"@type":113},"The review particularly emphasizes cancers with high metabolic activity and oxygen-rich environments, including hepatocellular carcinoma, renal cell carcinoma, and non-small-cell lung adenocarcinoma.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},365824,1790692598,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":26},2336474466712,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Review  \nClinical Significance of NUDT1 (MTH1) Across Cancer Types  \nRadosław Misiak 1, Karol Białkowski 2 and Ewelina Dondajewska 1, *  \nAcademic Editor: Maria Gazouli  \nReceived: 21 March 2025  \nRevised: 8 May 2025  \nAccepted: 9 May 2025  \nPublished: 27 May 2025  \nCitation: Misiak, R.; Białkowski, K.; Dondajewska, E. Clinical Significance of NUDT1 (MTH1) Across Cancer Types. Int. J. Mol. Sci. 2025, 26, 5137 .  \n[https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms26115137  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Department of Medical Biotechnology, Poznan University of Medical Sciences (PUMS), 61-701 Poznan, Poland  \n2 Department of Clinical Biochemistry, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toru ´n, 87-100 Bydgoszcz, Poland  \n* Correspondence: [dondajewska@ump.edu.pl](dondajewska@ump.edu.pl)  \nAbstract: MTH1 (MutT Homolog 1) protein is one of the enzymes that protect cells from mutagenetic actions of reactive oxygen species. It sanitizes the pool of free nucleotides, making sure that oxidized dNTPs are not incorporated into the DNA. Any misfunction of it would lead to mutations. As such, it has attracted interest of cancer researchers, and multiple studies have been conducted over the years to determine its role in tumor cells. It has been found that MTH1 is not downregulated in most tumor tissues but, to the contrary, often overexpressed. This suggests that MTH1 is used by cancer as an adaptation to increased oxidative stress caused by metabolic reprogramming to support excessive proliferation. Based on this premise, many recent studies have evaluated MTH1 as either prognostic factor, general biomarker or therapeutic target in cancer. Here, we summarize all available research on MTH1 mRNA, protein and its enzymatic activity in clinical samples across various cancer types, identifying a subset of cancers where MTH1 plays an important role. This is particularly evident in cancers characterized by high metabolic activity and oxygen-rich environments, such as hepatocellular carcinoma, renal cell carcinoma, or non-small cell lung adenocarcinoma.  \nKeywords: MTH1; NUDT1; oxidative stress; ROS response; prognostic factor; cancer  \n1. Introduction  \nReactive oxygen species (ROS) can cause oxidative damage in DNA and the cellular free-nucleotide pools (dNTPs and NTPs) . Some of the oxidatively damaged nucleotides, like the 8-oxo-7,8-dihydro-2′ -deoxyguanosine-5′ -triphosphate (8-oxo-dGTP), can be further incorporated into the DNA during replication, and are capable of ambiguous paring with canonical nucleobases. If these oxidized nucleotides are not removed, they can cause mutations in the subsequent replication rounds. 8-oxo-dGTP can pair with adenine and cytosine, leading to point mutations, in most cases AT→CG. Moreover, the direct formation of the 8-oxo-7,8-dihydroguanine (8-oxo-Gua) in double-stranded DNA may also lead to transversions, mostly GC→TA, which develop after two replication rounds (Figure 1) . To prevent an erroneous incorporation of oxidized DNA precursors and subsequent mutations, living organisms are equipped with a system of DNA protection enzymes. One of the main enzymes in this human system is the MTH1 (MutT Homolog 1) protein, coded by the NUDT1 gene [1] .  \nFigure 1. ROS can damage both nucleotides in free nucleotide pool, and nucleobases that are already part of a DNA strand. The nucleotide most prone to oxidation is 2′-deoxyguanosine-5′-triphosphate (dGTP) . The oxidized form—8-oxo-dGTP—can be mistakenly incorporated into DNA by polymerase and mispair with adenine, causing permanent mutation after the second replication round.  \nThe ","cbCaigLGrPSOwLKe","https://ap.wps.com/l/cbCaigLGrPSOwLKe","pdf",1503490,24,"English","# Introduction\n## ROS-induced nucleotide and DNA damage\n## DNA protection enzymes and the role of MTH1/NUDT1\n## Origin and characterization of MutT/NUDIX concept\n## NUDT1 gene and MTH1 protein features","[{\"question\":\"What is MTH1 (NUDT1) and what does it protect against?\",\"answer\":\"MTH1 is an enzyme that sanitizes the free nucleotide pool by preventing oxidized dNTPs from being incorporated into DNA, reducing the risk of mutations during replication.\"},{\"question\":\"Why is MTH1 important in cancer research?\",\"answer\":\"Cancer cells often show increased oxidative stress due to metabolic reprogramming, and MTH1 is frequently overexpressed, suggesting it supports survival and uncontrolled proliferation.\"},{\"question\":\"Which cancers are highlighted as showing important MTH1 involvement?\",\"answer\":\"The review particularly emphasizes cancers with high metabolic activity and oxygen-rich environments, including hepatocellular carcinoma, renal cell carcinoma, and non-small-cell lung adenocarcinoma.\"}]","Clinical Significance of NUDT1 (MTH1) Across Cancer Types - review | PDF",1790162537]