Chronologically modified androgen receptor in recurrent castration-resistant prostate cancer and its therapeutic targeting.

ABSTRACT: Resistance to second-generation androgen receptor (AR) antagonists such as enzalutamide is an inevitable consequence in patients with castration-resistant prostate cancer (CRPC). There are no effective therapeutic options for this recurrent disease. The expression of truncated AR variant 7 (AR-V7) has been suggested to be one mechanism of resistance; however, its low frequency in patients with CRPC does not explain the almost universal acquisition of resistance. We noted that the ability of AR to translocate to nucleus in an enzalutamide-rich environment opens up the possibility of a posttranslational modification in AR that is refractory to enzalutamide binding. Chemical proteomics in enzalutamide-resistant CRPC cells revealed acetylation at Lys⁶⁰⁹ in the zinc finger DNA bindin

SUBMITTER: Sawant M 

PROVIDER: S-EPMC10259236 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature