We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Targeting the N-Terminal Domain of the Androgen Receptor: A New Approach for the Treatment of Advanced Prostate Cancer.
- Authors
Antonarakis, Emmanuel S.; Chandhasin, Chandtip; Osbourne, Erica; Luo, Jun; Sadar, Marianne D.; Perabo, Frank
- Abstract
Despite the recent approval and widespread use of abiraterone acetate and enzalutamide for the treatment of castration-resistant prostate cancer (CRPC), this disease still poses significant management challenges because of various tumor escape mechanisms, including those that allow androgen receptor (AR) signaling to remain active. These AR-related resistance mechanisms include AR gene amplification or over-expression, constitutively active ligand-independent AR splice variants, and gain-of-function mutations involving the AR ligand-binding domain (LBD), among others. Therefore, the development of AR-targeted therapies that function independently of the LBD represents an unmet medical need and has the potential to overcome many of these resistance mechanisms. This article discusses N-terminal domain (NTD) inhibition as a novel concept in the field of AR-directed therapies for prostate cancer. AR NTD-targeting agents have the potential to overcome shortcomings of current hormonal therapies by inhibiting all forms of AR-mediated transcriptional activity, and as a result, may affect a broader AR population including mutational and splice variant ARs. Indeed, the first clinical trial of an AR NTD inhibitor is now underway.
- Subjects
ANTINEOPLASTIC agents; DOCETAXEL; ABIRATERONE acetate; ANDROGENS; COMBINED modality therapy; GENES; GENETIC mutation; PROSTATE tumors; DISEASE progression; THERAPEUTICS
- Publication
Oncologist, 2016, Vol 21, Issue 12, p1427
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1634/theoncologist.2016-0161