Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines.

ABSTRACT: Persistent androgen receptor (AR) transcriptional activity underlies resistance to AR-targeted therapy and progression to lethal castration-resistant prostate cancer (CRPC). Recent success in retargeting persistent AR activity with next generation androgen/AR axis inhibitors such as enzalutamide (MDV3100) has validated AR as a master regulator during all stages of disease progression. However, resistance to next generation AR inhibitors limits therapeutic efficacy for many patients. One emerging mechanism of CRPC progression is AR gene rearrangement, promoting synthesis of constitutively active truncated AR splice variants (AR-V) that lack the AR ligand-binding domain. In this study, we show that cells with AR gene rearrangements expressing both full-length and AR-Vs are androgen independe

SUBMITTER: Li Y 

PROVIDER: S-EPMC3549016 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature