In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. LB-097-LB-097
Abstract:
Expression of androgen receptor (AR) in prostate cancer (PCa) is heterogeneous but the functional significance of AR heterogeneity in regulating PCa biology and response to androgen/AR-targeted therapies remains unclear. Screening of ~200 castration-resistant PCa (CRPC) cores identified 3 AR expression patterns: nuclear (nuc-AR), mixed nuclear/cytoplasmic (nuc/cyto-AR), and low/no expression (AR-/lo). Xenograft CRPC modeling demonstrated that, although the AR+ CRPC responded to Enzalutamide, the AR-/lo CRPC was completely refractory to Enzalutamide. Genome editing-derived isogenic AR+ and AR-KO (knockout) PCa cells showed contrasting tumor-regenerating capacities and responses to castration and Enzalutamide. Whole-genome RNA-Seq and biochemical analyses coupled with experimental combinatorial therapy identified novel signaling pathways and BCL-2 as a critical therapeutic target in both AR+ and AR-/lo CRPC. Our study links AR heterogeneity to distinct castration/Enzalutamide responses and suggests the urgency in developing therapeutics to target AR-/lo PCa cells/clones. Citation Format: Qiuhui Li, Xin Chen, Qu Deng, Hsueh-Ping Chao, Amanda Tracz, Jason Kirk, Ruizhe Zhao, Kiera Rycaj, Dean G Tang. Linking prostate cancer cell AR heterogeneity to distinct castration and Enzalutamide responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-097.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2018-LB-097
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
