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Article ; Online: Epigenetic therapy in urologic cancers: an update on clinical trials.

Faleiro, Inês / Leão, Ricardo / Binnie, Alexandra / de Mello, Ramon Andrade / Maia, Ana-Teresa / Castelo-Branco, Pedro

Oncotarget

2016  Volume 8, Issue 7, Page(s) 12484–12500

Abstract: ... clinical trials (n=51) that test the efficacy of these drugs in patients with urologic cancers. The most ... 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 ...

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.
MeSH term(s) Azacitidine/therapeutic use ; Clinical Trials as Topic ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases/antagonists & inhibitors ; DNA (Cytosine-5-)-Methyltransferases/metabolism ; DNA Methylation/drug effects ; DNA Methyltransferase 3A ; Enzyme Inhibitors/therapeutic use ; Humans ; Male ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/enzymology ; Prostatic Neoplasms/genetics ; DNA Methyltransferase 3B
Chemical Substances DNMT3A protein, human ; Enzyme Inhibitors ; DNA (Cytosine-5-)-Methyltransferase 1 (EC 2.1.1.37) ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37) ; DNA Methyltransferase 3A (EC 2.1.1.37) ; Azacitidine (M801H13NRU)
Language English
Publishing date 2016-12-29
Publishing country United States
Document type Journal Article ; Review
ZDB-ID 2560162-3
ISSN 1949-2553 ; 1949-2553
ISSN (online) 1949-2553
ISSN 1949-2553
DOI 10.18632/oncotarget.14226
Database MEDical Literature Analysis and Retrieval System OnLINE

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