Oncotarget

Reviews:

Epigenetic therapy in urologic cancers: an update on clinical trials

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

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:12484-12500. https://doi.org/10.18632/oncotarget.14226

Metrics: PDF 1922 views  |   HTML 3423 views  |   ?  


Abstract

Inês Faleiro1,2,3, Ricardo Leão4,5, Alexandra Binnie1,2,3, Ramon Andrade de Mello1,2,3, Ana-Teresa Maia1,2,3 and Pedro Castelo-Branco1,2,3

1 Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal

2 Centre for Biomedical Research, University of Algarve, Faro, Portugal

3 Algarve Biomedical Center, Campus Gambelas, Edificio 2. Faro, Portugal

4 Department of Surgery, Princess Margaret Cancer Center, Division of Urology, University of Toronto, Toronto, Canada

5 Renal Transplantation and Urology Service, Coimbra University Hospital Center EPE, Faculty of Medicine, University of Coimbra, Portugal

Correspondence to:

Pedro Castelo-Branco, email:

Keywords: epigenetic therapy, urologic cancers, clinical trials

Received: October 26, 2016 Accepted: December 13, 2016 Published: December 26, 2016

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 14226