title: Epigenetic therapy in urologic cancers: an update on clinical trials.
abstract: Epigenetic dysregulation is one of many factors that contribute to cancer development and progression. Numerous epigenetic alterations have been identified in urologic cancers including histone modifications, DNA methylation changes, and microRNA expression. Since these changes are reversible, efforts are being made to develop epigenetic drugs that restore the normal epigenetic patterns of cells, and many clinical trials are already underway to test their clinical potential. In this review we analyze multiple clinical trials (n=51) that test the efficacy of these drugs in patients with urologic cancers. The most frequently used epigenetic drugs were histone deacetylase inhibitors followed by antisense oligonucleotides, DNA methyltransferase inhibitors and histone demethylase inhibitors, the last of which are only being tested in prostate cancer. In more than 50% of the clinical trials considered, epigenetic drugs were used as part of combination therapy, which achieved the best results. The epigenetic regulation of some cancers is still matter of research but will undoubtedly open a window to new therapeutic approaches in the era of personalized medicine. The future of therapy for urological malignancies is likely to include multidrug regimens in which epigenetic modifying drugs will play an important role.
authors.affiliation: Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.|Centre for Biomedical Research, University of Algarve, Faro, Portugal.|Algarve Biomedical Center, Campus Gambelas, Edificio 2. Faro, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Faleiro
authors.affiliation: Department of Surgery, Princess Margaret Cancer Center, Division of Urology, University of Toronto, Toronto, Canada.|Renal Transplantation and Urology Service, Coimbra University Hospital Center EPE, Faculty of Medicine, University of Coimbra, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Leão
authors.affiliation: Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.|Centre for Biomedical Research, University of Algarve, Faro, Portugal.|Algarve Biomedical Center, Campus Gambelas, Edificio 2. Faro, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Binnie
authors.affiliation: Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.|Centre for Biomedical Research, University of Algarve, Faro, Portugal.|Algarve Biomedical Center, Campus Gambelas, Edificio 2. Faro, Portugal.
authors.forename: Ramon Andrade
authors.initials: RA
authors.lastname: de Mello
authors.affiliation: Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.|Centre for Biomedical Research, University of Algarve, Faro, Portugal.|Algarve Biomedical Center, Campus Gambelas, Edificio 2. Faro, Portugal.
authors.forename: Ana-Teresa
authors.initials: AT
authors.lastname: Maia
authors.affiliation: Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.|Centre for Biomedical Research, University of Algarve, Faro, Portugal.|Algarve Biomedical Center, Campus Gambelas, Edificio 2. Faro, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Castelo-Branco
mesh_terms: D001374:Azacitidine / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D000090205:DNA Methyltransferase 3A; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000097584:DNA Methyltransferase 3B
chemical_list: D001374:Azacitidine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D004791:Enzyme Inhibitors; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human
keywords: clinical trials; epigenetic therapy; urologic cancers