Investigating Genomic Mechanisms of Treatment Resistance in Castration Resistant Prostate Cancer
Abstract
The purpose of this work is to better understand the mechanisms of resistance to androgen biosynthesis inhibitors in men with castration resistant prostate cancer, and to investigate clinical methods of overcoming resistance. CTCs collected in 41 men with abiraterone-na ve mCRPC at baseline, and in 12 of these men at the time of clinical resistance to abiraterone. Cells have been enumerated for CTCs, CTC clusters, CTCs expressing stem-like and mesenchymal markers. We have optimized methods for extracting DNA and performing array comparative genomic hybridization (aCGH). Currently we are in the process of analyzing the aCGH results in collaboration with the UCSF Biostatics Core. We have observed that there is a wide spectrum of CTC diversity (epithelial-like, mesenchymal, stem-like) in men starting abiraterone. Correlations of this diversity with clinical outcome are underway. Phase II protocol for Dose-Increased Abiraterone Acetate in Men with mCRPC (PI: Friedlander) fully accrued at UCSF (n=21) and Oregon Health Sciences University (n=20). Phase I protocol of Abiraterone Acetate plus ARN-509 in men with mCRPC (PI: Friedlander) set to open at UCSF in mid-late 2014. Integration of both clinical trials with Stand Up 2 Cancer West Coast Dream Team castration-resistant prostate cancer biopsy protocol. Analysis of CTC-biopsy correlations underway.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2014
- Accession Number
- ADA606110
Entities
People
- Terence W. Friedlander
Organizations
- University of California, San Francisco