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Increasing evidence links chronodisruption with aberrant functionality in clock gene expression, resulting in multiple diseases, including cancer. In this context, tumor cells have an altered circadian machinery compared to normal cells, which deregulates the cell cycle, repair mechanisms, energy metabolism and other processes. Melatonin is the main hormone produced by the pineal gland, whose production and secretion oscillates in accordance with the light:dark cycle. In addition, melatonin regulates the expression of clock genes, including those in cancer cells, which could play a key role in the numerous oncostatic effects of this hormone. This review aims to describe and clarify the role of clock genes in cancer, as well as the possible mechanisms of the action of melatonin through which it regulates the expression of the tumor\u2019s circadian machinery, in order to propose future anti-neoplastic clinical treatments.<\/jats:p>","DOI":"10.3390\/ijms24031919","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T02:51:37Z","timestamp":1674096697000},"page":"1919","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Role of Melatonin in Cancer: Effect on Clock Genes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5345-1356","authenticated-orcid":false,"given":"C\u00e9sar","family":"Rodr\u00edguez-Santana","sequence":"first","affiliation":[{"name":"Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7541-4898","authenticated-orcid":false,"given":"Javier","family":"Florido","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mart\u00ednez-Ruiz","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"L\u00f3pez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9680-1560","authenticated-orcid":false,"given":"Dar\u00edo","family":"Acu\u00f1a-Castroviejo","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain"},{"name":"Department of Physiology, Faculty of Medicine, University of Granada, 18071 Granada, Spain"},{"name":"CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Instituto de Investigaci\u00f3n Biosanitaria Ibs., 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1256-7656","authenticated-orcid":false,"given":"Germaine","family":"Escames","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain"},{"name":"Department of Physiology, Faculty of Medicine, University of Granada, 18071 Granada, Spain"},{"name":"CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Instituto de Investigaci\u00f3n Biosanitaria Ibs., 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3282","DOI":"10.4161\/15384101.2014.954454","article-title":"Loss of Circadian Clock Gene Expression Is Associated with Tumor Progression in Breast Cancer","volume":"13","author":"Cadenas","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1007\/s00018-014-1579-2","article-title":"Extrapineal Melatonin: Sources, Regulation, and Potential Functions","volume":"71","author":"Escames","year":"2014","journal-title":"Cell. 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