| Autor: |
Antonarakis, Emmanuel S., Chandhasin, Chandtip, Osbourne, Erica, Luo, Jun, Sadar, Marianne D., Perabo, Frank |
| Předmět: |
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| Zdroj: |
Oncologist; Dec2016, Vol. 21 Issue 12, p1427-1435, 9p, 2 Diagrams, 1 Chart |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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