Validation of histone deacetylase 3 as a therapeutic target in castration‐resistant prostate cancer
Abstract
Whereas the androgen receptor (AR) signaling axis remains a therapeutic target in castration‐resistant prostate cancer (CRPC), the emergence of AR mutations and splice variants as mechanisms underlying resistance to contemporary inhibitors of this pathway highlights the need for new therapeutic approaches to target this disease. Of significance in this regard is the considerable preclinical data, indicating that histone deacetylase (HDAC) inhibitors may have utility in the treatment of CRPC. However, the results of clinical studies using HDAC inhibitors (directed against HDAC1, 2, 3, and 8) in CRPC are equivocal, a result that some have attributed to their ability to induce an epithelial to mesenchymal transition (EMT) and neuroendocrine differentiation. We posited that it might be possible to uncouple the beneficial effects of HDAC inhibitors on AR signaling from their undesired activities by targeting specific HDACs as opposed to using the pan‐inhibitor strategy that has been employed to date.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 15, 2017
- Source ID
- 10.1002/pros.23467
Entities
People
- Abigail B. Mcleod
- Ching‐yi Chang
- Donald P McDonnell
- Holly M. Alley
- James P. Stice
- Suzanne E Wardell
Organizations
- Congressionally Directed Medical Research Programs
- Duke University
- National Cancer Institute