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Kaushik D, Vashistha V, Isharwal S, et al. Histone deacetylase inhibitors in castration-resistant prostate cancer: molecular mechanism of action and recent clinical trials. Ther Adv Urol. 2015;7(6):388-95doi: 10.1177/1756287215597637.
Kaushik, D., Vashistha, V., Isharwal, S., Sediqe, S. A., & Lin, M. F. (2015). Histone deacetylase inhibitors in castration-resistant prostate cancer: molecular mechanism of action and recent clinical trials. Therapeutic advances in urology, 7(6), 388-95. https://doi.org/10.1177/1756287215597637
Kaushik, Dharam, et al. "Histone deacetylase inhibitors in castration-resistant prostate cancer: molecular mechanism of action and recent clinical trials." Therapeutic advances in urology vol. 7,6 (2015): 388-95. doi: https://doi.org/10.1177/1756287215597637
Kaushik D, Vashistha V, Isharwal S, Sediqe SA, Lin MF. Histone deacetylase inhibitors in castration-resistant prostate cancer: molecular mechanism of action and recent clinical trials. Ther Adv Urol. 2015 Dec;7(6):388-95. doi: 10.1177/1756287215597637. PMID: 26622323; PMCID: PMC4647138.
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Ther Adv Urol. 2015 Dec;7(6):388-95. doi: 10.1177/1756287215597637.

Histone deacetylase inhibitors in castration-resistant prostate cancer: molecular mechanism of action and recent clinical trials.

Therapeutic advances in urology

Dharam Kaushik, Vishal Vashistha, Sudhir Isharwal, Soud A Sediqe, Ming-Fong Lin

Affiliations

  1. Department of Urology, University of Texas Health Science Center and Cancer Therapy and Research Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
  2. Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA.
  3. Section of Urology, University of Nebraska Medical Center, Omaha, NE, USA.
  4. Department of Internal Medicine, MetroHealth Medical Center, Cleveland, OH, USA.
  5. Section of Urology, and Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE, USA.

PMID: 26622323 PMCID: PMC4647138 DOI: 10.1177/1756287215597637

Abstract

Historically, androgen-deprivation therapy has been the cornerstone for treatment of metastatic prostate cancer. Unfortunately, nearly majority patients with prostate cancer transition to the refractory state of castration-resistant prostate cancer (CRPC). Newer therapeutic agents are needed for treating these CRPC patients that are unresponsive to androgen deprivation and/or chemotherapy. The histone deacetylase (HDAC) family of enzymes limits the expression of genomic regions by improving binding between histones and the DNA backbone. Modulating the role of HDAC enzymes can alter the cell's regulation of proto-oncogenes and tumor suppressor genes, thereby regulating potential neoplastic proliferation. As a result, histone deacetylase inhibitors (HDACi) are now being evaluated for CRPC or chemotherapy-resistant prostate cancer due to their effects on the expression of the androgen receptor gene. In this paper, we review the molecular mechanism and functional target molecules of different HDACi as applicable to CRPC as well as describe recent and current clinical trials involving HDACi in prostate cancer. To date, four HDAC classes comprising 18 isoenzymes have been identified. Recent clinical trials of vorinostat, romidepsin, and panobinostat have provided cautious optimism towards improved outcomes using these novel therapeutic agents for CPRC patients. Nevertheless, no phase III trial has been conducted to cement one of these drugs as an adjunct to androgen-deprivation therapy. Consequently, further investigation is necessary to delineate the benefits and drawbacks of these medications.

Keywords: castration-resistant prostate cancer; clinical trials; histone deacetylase inhibitors

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