Abiraterone treatment in castration-resistant prostate cancer selects for progesterone responsive mutant androgen receptors.

ABSTRACT:

Purpose

The CYP17A1 inhibitor abiraterone markedly reduces androgen precursors and is thereby effective in castration-resistant prostate cancer (CRPC). However, abiraterone increases progesterone, which can activate certain mutant androgen receptors (AR) identified previously in flutamide-resistant tumors. Therefore, we sought to determine if CYP17A1 inhibitor treatment selects for progesterone-activated mutant ARs.

Experimental design

AR was examined by targeted sequencing in metastatic tumor biopsies from 18 patients with CRPC who were progressing on a CYP17A1 inhibitor (17 on abiraterone, 1 on ketoconazole), alone or in combination with dutasteride, and by whole-exome sequencing in residual tumor in one patient treated with neoadjuvant leuprolide plus abiraterone.

Resu

SUBMITTER: Chen EJ 

PROVIDER: S-EPMC4359958 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature