Molecular Indicators of Castration-Resistant Prostate Cancer
Abstract
Metastatic prostate cancers are commonly treated by agents designed to suppress androgen receptor (AR) signaling mediated by the full-length AR (AR-FL). Why some patients progress rapidly after treatment while others benefit with prolonged remission is an unsolved question. We propose approaches to develop molecular indicators of response and resistance that will enable prediction (before therapy) or early detection (during therapy) of therapeutic benefit. We will test the hypothesis that AR splice variants (AR-Vs) are molecular indicators of castration-resistant prostate cancer (CRPC). During this funding period, we achieved a major milestone by completing RNA sequencing of 48 CRPC specimens and publishing data on 4 specimens focusing on the analysis of transcriptional programs mediated by one of most important AR-Vs, AR-V7. We achieved another major milestone by establishing an association of AR-V7 with resistance to two major therapies targeting the androgen axis. We conclude that detection of AR-V7 predicts treatment outcome in men with metastatic castration-resistant prostate cancer initiating AR-targeting therapies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA613605
Entities
People
- Jun Luo
Organizations
- Johns Hopkins University