{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:20:56Z","timestamp":1787656856377,"version":"build-2736575974"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Guangdong Medical Science and Technology Research Fund Project","award":["A2022464"],"award-info":[{"award-number":["A2022464"]}]},{"name":"the High-level Hospital Construction Research Project of Maoming People's Hospital, and the Maoming Municipal Science and Technology Bureau Special Plan","award":["2020KJZX018"],"award-info":[{"award-number":["2020KJZX018"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int Urol Nephrol"],"DOI":"10.1007\/s11255-026-05096-2","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T19:39:30Z","timestamp":1773430770000},"page":"3471-3481","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The MTH1 inhibitor TH287 sensitized Castration-Resistant Prostate Cancer cells to ionizing radiation therapy"],"prefix":"10.1007","volume":"58","author":[{"given":"Yuan","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingbang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifeng","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqiu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"5096_CR1","first-page":"990","volume":"3","author":"F Saad","year":"2015","unstructured":"Saad F, Chi KN, Finelli A, Hotte SJ, Izawa J, Kapoor A, Kassouf W, Loblaw A, North S, Rendon R, So A, Usmani N, Vigneault E, Fleshner NE (2015) The 2015 CUA-CUOG guidelines for the management of Castration-Resistant Prostate Cancer (CRPC). Can Urol Assoc J 3:990\u2013996","journal-title":"Can Urol Assoc J"},{"key":"5096_CR2","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s10689-021-00227-3","volume":"21","author":"H Raghallaigh","year":"2022","unstructured":"Raghallaigh H, Eeles R (2022) Genetic predisposition to prostate cancer: an update. Fam Cancer 21:101\u2013114","journal-title":"Fam Cancer"},{"key":"5096_CR3","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1200\/GO.20.00511","volume":"7","author":"FC Maluf","year":"2021","unstructured":"Maluf FC, Pereira FMT, Silva AG, Dettino ALA, Cardoso APG, Sasse AS, Soares A, Kann AG, Herchenhorn D, Jardim DLF, Cort\u00e9s DEL, Kater FR, Morbeck IAP, Reolon JFN, Rinck JA Jr, Zarb\u00e1 JJ, Sade JP, da Trindade KM, Costa LAGA, Dos Santos LV, Maia MC, Siqueira MB, Gillessen S (2021) Consensus on the treatment and follow-up for metastatic castration-resistant prostate cancer: a report from the first global prostate cancer consensus conference for developing countries (PCCCDC). JCO Glob Oncol 7:559\u2013571","journal-title":"JCO Glob Oncol"},{"key":"5096_CR4","first-page":"365","volume":"4","author":"T Chandrasekar","year":"2015","unstructured":"Chandrasekar T, Yang JC, Gao AC, Evans CP (2015) Mechanisms of Resistance in Castration-Resistant Prostate Cancer (CRPC). Transl Androl Urol 4:365","journal-title":"Transl Androl Urol"},{"key":"5096_CR5","doi-asserted-by":"publisher","first-page":"103370","DOI":"10.1016\/j.critrevonc.2021.103370","volume":"163","author":"D Tong","year":"2021","unstructured":"Tong D (2021) Unravelling the molecular mechanisms of prostate cancer evolution from genotype to phenotype. Crit Rev Oncol Hematol 163:103370","journal-title":"Crit Rev Oncol Hematol"},{"key":"5096_CR6","first-page":"232","volume":"22","author":"C Huggins","year":"1972","unstructured":"Huggins C, Hodges CV (1972) Studies on prostatic cancer.I. the effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin 22:232\u2013240","journal-title":"CA Cancer J Clin"},{"key":"5096_CR7","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/pcan.2014.35","volume":"17","author":"A Patrikidou","year":"2014","unstructured":"Patrikidou A, Loriot Y, Eymard JC, Albiges L, Massard C, Ileana E, Di Palma M, Escudier B, Fizazi K (2014) Who dies from prostate cancer? Prostate Cancer Prostatic Dis 17:348\u2013352","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"5096_CR8","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1159\/000519861","volume":"100","author":"V Achard","year":"2022","unstructured":"Achard V, Putora PM, Omlin A, Zilli T, Fischer S (2022) Metastatic prostate cancer: treatment options. Oncology 100:48\u201359","journal-title":"Oncology"},{"key":"5096_CR9","doi-asserted-by":"publisher","first-page":"5733","DOI":"10.1158\/0008-5472.CAN-21-0061","volume":"81","author":"K Sanjiv","year":"2021","unstructured":"Sanjiv K, Calder\u00f3n-Monta\u00f1o JM, Pham TM, Erkers T, Tsuber V, Alml\u00f6f I, H\u00f6glund A, Heshmati Y, Seashore-Ludlow B, Nagesh Danda A, Gad H, Wiita E, G\u00f6kt\u00fcrk C, Rasti A, Friedrich S, Centio A, Estruch M, V\u00e5tsveen TK, Struyf N, Visnes T, Scobie M, Koolmeister T, Henriksson M, Wallner O, Sandvall T, Lehmann S, Theilgaard-M\u00f6nch K, Garnett MJ, \u00d6stling P, Walfridsson J, Helleday T, Warpman BU (2021) MTH1 inhibitor TH1579 induces oxidative DNA damage and mitotic arrest in acute myeloid leukemia. Cancer Res 81:5733\u20135744","journal-title":"Cancer Res"},{"key":"5096_CR10","doi-asserted-by":"publisher","DOI":"10.1101\/575290","author":"H Gad","year":"2019","unstructured":"Gad H, Mortusewics O, Rudd SG, Stolz A, Maral N, Brautigam L (2019) MTH1 promotes mitotic progression to avoid oxidative DNA damage in cancer cells. BioRxiv. https:\/\/doi.org\/10.1101\/575290","journal-title":"BioRxiv"},{"key":"5096_CR11","doi-asserted-by":"publisher","first-page":"102704","DOI":"10.1016\/j.ebiom.2020.102704","volume":"53","author":"B Moukengue","year":"2020","unstructured":"Moukengue B, Brown HK, Charrier C, Battaglia S, Baud\u2019Huin M, Quillard T (2020) TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model. EBioMedicine 53:102704","journal-title":"EBioMedicine"},{"key":"5096_CR12","first-page":"3240","volume":"15","author":"F Ikejiri","year":"2018","unstructured":"Ikejiri F, Honma Y, Kasukabe T, Urano T, Suzumiya J (2018) TH588, an MTH1 inhibitor, enhances phenethyl isothiocyanate-induced growth inhibition in pancreatic cancer cells. Oncol Lett 15:3240\u20133244","journal-title":"Oncol Lett"},{"key":"5096_CR13","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/s41598-018-37316-w","volume":"9","author":"LM van der Waals","year":"2019","unstructured":"van der Waals LM, Laoukili J, Jongen JMJ, Raats DA, Borel Rinkes IHM, Kranenburg O (2019) Differential anti-tumour effects of MTH1 inhibitors in patient-derived 3D colorectal cancer cultures. Sci Rep 9:819","journal-title":"Sci Rep"},{"key":"5096_CR14","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.dnarep.2015.05.008","volume":"33","author":"E Coskun","year":"2015","unstructured":"Coskun E, Jaruga P, Jemth AS, Loseva O, Scanlan LD, Tona A, Lowenthal MS, Helleday T, Dizdaroglu M (2015) Addiction to MTH1 protein results in intense expression in human breast cancer tissue as measured by liquid chromatography-isotope-dilution tandem mass spectrometry. DNA Repair 33:101\u2013110","journal-title":"DNA Repair"},{"key":"5096_CR15","doi-asserted-by":"publisher","first-page":"8860","DOI":"10.3390\/ijms21228860","volume":"21","author":"H Chen","year":"2020","unstructured":"Chen H, Afrin S, Guo Y, Chu W, Benzinger TLS, Rogers BE, Garbow JR, Perlmutter JS, Zhou D, Xu J (2020) Radiolabeled 6-(2, 3-Dichlorophenyl)-N4-Methylpyrimidine-2, 4-Diamine (TH287): a potential radiotracer for measuring and imaging MTH1. Int J Mol Sci 21:8860","journal-title":"Int J Mol Sci"},{"key":"5096_CR16","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/nature13194","volume":"508","author":"KV Huber","year":"2014","unstructured":"Huber KV, Salah E, Radic B, Gridling M, Elkins JM, Stukalov A, Jemth AS, G\u00f6kt\u00fcrk C, Sanjiv K, Str\u00f6mberg K, Pham T, Berglund UW, Colinge J, Bennett KL, Loizou JI, Helleday T, Knapp S, Superti-Furga G (2014) Stereospecific targeting of MTH1 by (S)-Crizotinib as an anticancer strategy. Nature 508:222\u2013227","journal-title":"Nature"},{"key":"5096_CR17","doi-asserted-by":"publisher","first-page":"62","DOI":"10.3892\/ol.2020.12324","volume":"21","author":"M Hu","year":"2021","unstructured":"Hu M, Ning J, Mao L, Yu Y, Wu Y (2021) Antitumour activity of TH1579, a novel MTH1 inhibitor, against castration-resistant prostate cancer. Oncol Lett 21:62","journal-title":"Oncol Lett"},{"key":"5096_CR18","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1186\/s12885-018-5095-x","volume":"18","author":"M Pompsch","year":"2018","unstructured":"Pompsch M, Vogel J, Classen F, Kranz P, Iliakis G, Riffkin H, Brockmeier U, Metzen E (2018) The presumed MTH1-inhibitor TH588 sensitizes colorectal carcinoma cells to ionizing radiation in hypoxia. BMC Cancer 18:1190","journal-title":"BMC Cancer"},{"key":"5096_CR19","doi-asserted-by":"publisher","first-page":"e0178375","DOI":"10.1371\/journal.pone.0178375","volume":"12","author":"ET Aristizabal Prada","year":"2017","unstructured":"Aristizabal Prada ET, Orth M, N\u00f6lting S, Sp\u00f6ttl G, Maurer J, Auernhammer C (2017) The MTH1 inhibitor TH588 demonstrates anti-tumoral effects alone and in combination with Everolimus, 5-FU, and gamma-irradiation in neuroendocrine tumor cells. PLoS ONE 12:e0178375","journal-title":"PLoS ONE"},{"key":"5096_CR20","doi-asserted-by":"publisher","first-page":"27547","DOI":"10.18632\/oncotarget.25547","volume":"9","author":"Z Versano","year":"2018","unstructured":"Versano Z, Shany E, Freedman S, Tuval-Kochen L, Leitner M, Paglin S, Toren A, Yalon M (2018) MutT homolog 1 counteracts the effect of anti-neoplastic treatments in adult and pediatric Glioblastoma cells. Oncotarget 9:27547\u201327563","journal-title":"Oncotarget"},{"key":"5096_CR21","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3390\/ijms17010102","volume":"17","author":"P Maier","year":"2016","unstructured":"Maier P, Hartmann L, Wenz F, Herskind C (2016) Cellular pathways in response to ionizing radiation and their targetability for tumor radiosensitization. Int J Mol Sci 17:102","journal-title":"Int J Mol Sci"},{"key":"5096_CR22","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/php.12668","volume":"93","author":"J Hu","year":"2017","unstructured":"Hu J, Adar S (2017) The cartography of UV-induced DNA damage formation and DNA repair. Photochem Photobiol 93:199\u2013206","journal-title":"Photochem Photobiol"},{"key":"5096_CR23","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1002\/em.22176","volume":"59","author":"AQ Khan","year":"2018","unstructured":"Khan AQ, Travers JB, Kemp MG (2018) Roles of UVA radiation and DNA damage responses in melanoma pathogenesis. Environ Mol Mutagen 59:438\u2013460","journal-title":"Environ Mol Mutagen"},{"key":"5096_CR24","doi-asserted-by":"publisher","first-page":"496","DOI":"10.3390\/ijms19020496","volume":"19","author":"A Gerelchuluun","year":"2018","unstructured":"Gerelchuluun A, Maeda J, Manabe E, Brents CA, Sakae T, Fujimori A, Chen DJ, Tsuboi K, Kato TA (2018) Histone deacetylase inhibitor induced radiation sensitization effects on human cancer cells after photon and hadron radiation exposure. Int J Mol Sci 19:496","journal-title":"Int J Mol Sci"},{"key":"5096_CR25","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s12013-016-0734-9","volume":"74","author":"H Kayhan","year":"2016","unstructured":"Kayhan H, Esmekaya MA, Saglam AS, Tuysuz MZ, Canseven AG, Yagci AM, Seyhan N (2016) Does MW radiation affect gene expression, apoptotic level, and cell cycle progression of human SH-SY5Y neuroblastoma cells? Cell Biochem Biophys 74:99\u2013107","journal-title":"Cell Biochem Biophys"},{"key":"5096_CR26","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.radonc.2011.05.055","volume":"101","author":"PL Olive","year":"2011","unstructured":"Olive PL (2011) Retention of \u03b3H2AX foci as an indication of lethal DNA damage. Radiother Oncol 101:18\u201323","journal-title":"Radiother Oncol"},{"key":"5096_CR27","doi-asserted-by":"publisher","first-page":"376","DOI":"10.3892\/ol.2021.12637","volume":"21","author":"YY Segura-Moreno","year":"2021","unstructured":"Segura-Moreno YY, Sanabria-Salas MC, Varela R, Mesa JA, Serrano ML (2021) Decoding the heterogeneous landscape in the development prostate cancer. Oncol Lett 21:376","journal-title":"Oncol Lett"},{"key":"5096_CR28","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.neo.2020.09.002","volume":"22","author":"JE Vellky","year":"2020","unstructured":"Vellky JE, William AR (2020) Development and prevalence of castration-resistant prostate cancer subtypes. Neoplasia 22:566\u2013575","journal-title":"Neoplasia"},{"key":"5096_CR29","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.3390\/cancers13102426","volume":"13","author":"S Gleicher","year":"2021","unstructured":"Gleicher S, Porter BA, Nath D, Li G, Khanna R, Goldberg H, Kortylewski M, Bratslavsky G, Kotula L (2021) Novel target opportunities in non-metastatic castrate resistant prostate cancer. Cancers (Basel) 13:2426","journal-title":"Cancers (Basel)"},{"issue":"3","key":"5096_CR30","first-page":"223","volume":"35","author":"D Zhan","year":"2020","unstructured":"Zhan D et al (2020) MTH1 inhibitor TH287 suppresses gastric cancer development through the regulation of PI3K\/AKT signaling. Cancer Biother Radiopharm 35(3):223\u2013232","journal-title":"Cancer Biother Radiopharm"},{"key":"5096_CR31","doi-asserted-by":"publisher","first-page":"102704","DOI":"10.1016\/j.ebiom.2020.102704","volume":"53","author":"B Moukengue","year":"2020","unstructured":"Moukengue B et al (2020) TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model. EBioMedicine 53:102704","journal-title":"EBioMedicine"},{"issue":"1","key":"5096_CR32","doi-asserted-by":"publisher","first-page":"6317","DOI":"10.1038\/s41598-021-85613-8","volume":"11","author":"MP Oksvold","year":"2021","unstructured":"Oksvold MP et al (2021) Karonudib has potent anti-tumor effects in preclinical models of B-cell lymphoma. Sci Rep 11(1):6317","journal-title":"Sci Rep"},{"key":"5096_CR33","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1667\/RR1399.1","volume":"170","author":"T Sangsuwan","year":"2008","unstructured":"Sangsuwan T, Haghdoost S (2008) The nucleotide pool, a target for low-dose gamma-ray-induced oxidative stress. Radiat Res 170:776\u2013783","journal-title":"Radiat Res"},{"issue":"4","key":"5096_CR34","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1111\/j.1349-7006.2007.00409.x","volume":"98","author":"T Tsuzuki","year":"2007","unstructured":"Tsuzuki T, Nakatsu Y, Nakabeppu Y (2007) Significance of error-avoiding mechanisms for oxidative DNA damage in carcinogenesis. Cancer Sci 98(4):465\u2013470","journal-title":"Cancer Sci"},{"key":"5096_CR35","doi-asserted-by":"publisher","first-page":"5479","DOI":"10.1158\/1078-0432.CCR-10-3297","volume":"18","author":"N Somaiah","year":"2012","unstructured":"Somaiah N, Yarnold J, Daley F, Pearson A, Gothard L, Rothkamm K, Helleday T (2012) The relationship between homologous recombination repair and the sensitivity of human epidermis to the size of daily doses over a 5-week course of breast radiotherapy. Clin Cancer Res 18:5479\u20135488","journal-title":"Clin Cancer Res"},{"key":"5096_CR36","doi-asserted-by":"publisher","first-page":"103243","DOI":"10.1016\/j.dnarep.2021.103243","volume":"108","author":"N Rahmanian","year":"2021","unstructured":"Rahmanian N, Shokrzadeh M, Eskandani M (2021) Recent advances in \u03b3H2AX biomarker-based genotoxicity assays: a marker of DNA damage and repair. DNA Repair (Amst) 108:103243","journal-title":"DNA Repair (Amst)"},{"key":"5096_CR37","doi-asserted-by":"publisher","first-page":"7198","DOI":"10.3390\/molecules26237198","volume":"26","author":"A Merighi","year":"2021","unstructured":"Merighi A, Gionchiglia N, Granato A, Lossi L (2021) The phosphorylated form of the histone H2AX (\u03b3H2AX) in the brain from embryonic life to old age. Molecules 26:7198","journal-title":"Molecules"},{"issue":"1","key":"5096_CR38","doi-asserted-by":"publisher","first-page":"14667","DOI":"10.1038\/s41598-019-51205-w","volume":"9","author":"N Gul","year":"2019","unstructured":"Gul N et al (2019) The MTH1 inhibitor TH588 is a microtubule-modulating agent that eliminates cancer cells by activating the mitotic surveillance pathway. Sci Rep 9(1):14667","journal-title":"Sci Rep"},{"issue":"1","key":"5096_CR39","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.cels.2019.05.009","volume":"9","author":"JC Patterson","year":"2019","unstructured":"Patterson JC et al (2019) VISAGE reveals a targetable mitotic spindle vulnerability in cancer cells. Cell Syst 9(1):74-92.e8","journal-title":"Cell Syst"},{"issue":"1","key":"5096_CR40","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/s41598-018-37316-w","volume":"9","author":"LM van der Waals","year":"2019","unstructured":"van der Waals LM et al (2019) Differential anti-tumour effects of MTH1 inhibitors in patient-derived 3D colorectal cancer cultures. Sci Rep 9(1):819","journal-title":"Sci Rep"},{"issue":"12","key":"5096_CR41","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1080\/09168451.2019.1648207","volume":"83","author":"JW Lee","year":"2019","unstructured":"Lee JW et al (2019) Antitumor effects of MutT homolog 1 inhibitors in human bladder cancer cells. Biosci Biotechnol Biochem 83(12):2265\u20132271","journal-title":"Biosci Biotechnol Biochem"}],"container-title":["International Urology and Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11255-026-05096-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11255-026-05096-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11255-026-05096-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:40:53Z","timestamp":1787654453000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11255-026-05096-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["5096"],"URL":"https:\/\/doi.org\/10.1007\/s11255-026-05096-2","relation":{},"ISSN":["1573-2584"],"issn-type":[{"value":"1573-2584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]},"assertion":[{"value":"12 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that there are no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}