{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T20:26:18Z","timestamp":1776284778141,"version":"3.50.1"},"reference-count":173,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["SAF2015-66015-R"],"award-info":[{"award-number":["SAF2015-66015-R"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["PID2019-110758RB-I00"],"award-info":[{"award-number":["PID2019-110758RB-I00"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RETIC no. RD12\/0036\/0009"],"award-info":[{"award-number":["RETIC no. RD12\/0036\/0009"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CIBERONC no. CB16\/12\/00228"],"award-info":[{"award-number":["CIBERONC no. CB16\/12\/00228"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/ 144241\/2019"],"award-info":[{"award-number":["SFRH\/BD\/ 144241\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Bladder cancer (BC) is the tenth most frequent cancer worldwide and is associated with high mortality when diagnosed in its most aggressive form, which is not reverted by the current treatment options. Thus, the development of new therapeutic strategies, either alternative or complementary to the current ones, is of major importance. The disruption of normal epigenetic mechanisms, namely, DNA methylation, is a known early event in cancer development. Consequently, DNA methyltransferase (DNMT) inhibitors constitute a promising therapeutic target for the treatment of BC. Although these inhibitors, mainly nucleoside analogues such as 5-azacytidine (5-aza) and decitabine (DAC), cause re-expression of tumor suppressor genes, inhibition of tumor cell growth, and increased apoptosis in BC experimental models and clinical trials, they also show important drawbacks that prevent their use as a valuable option for the treatment of BC. However, their combination with chemotherapy and\/or immune-checkpoint inhibitors could aid in their implementation in the clinical practice. Here, we provide a comprehensive review of the studies exploring the effects of DNA methylation inhibition using DNMTs inhibitors in BC, from in vitro and in vivo studies to clinical trials.<\/jats:p>","DOI":"10.3390\/cells9081850","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T07:25:03Z","timestamp":1597044303000},"page":"1850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["DNA Methylation as a Therapeutic Target for Bladder Cancer"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4466-037X","authenticated-orcid":false,"given":"Sandra P.","family":"Nunes","sequence":"first","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal"},{"name":"Molecular Oncology Unit, Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT), 28040 Madrid, Spain"},{"name":"Biomedical Research Institute I+12, University Hospital \u201c12 de Octubre\u201d, 28041 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-4666","authenticated-orcid":false,"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal"},{"name":"Department of Pathology, Portuguese Oncology Institute of Porto, 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar\u2014University of Porto (ICBAS-UP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[{"name":"Cancer Biology &amp; Epigenetics Group-Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), 4200-072 Porto, Portugal"},{"name":"Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar\u2014University of Porto (ICBAS-UP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7520-3177","authenticated-orcid":false,"given":"Jes\u00fas M.","family":"Paramio","sequence":"additional","affiliation":[{"name":"Molecular Oncology Unit, Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas (CIEMAT), 28040 Madrid, Spain"},{"name":"Biomedical Research Institute I+12, University Hospital \u201c12 de Octubre\u201d, 28041 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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