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. Key Accomplishments and Findings to date: Primary endpoint of Phase II study of Dose-Increased Abiraterone Acetate in Men with mCRPC (PI: Friedlander) met, showing that increase in dose of abiraterone at the time of clinical resistance does not result in second PSA declines. This data was presented at the 2015 ASCO Genitourinary Symposium (Orlando, FL). Manuscript currently in process. CTCs collected in 38 men with abiraterone-na ve mCRPC at baseline on the aforementioned study. Cells have been enumerated for CTCs, CTC clusters, CTCs expressing stem-like and epithelial markers. A trend towards higher CTC counts was observed in patients who were primarily refractory to abiraterone acetate. Patients with more CTC clusters were more likely to have longer responses to abiraterone acetate (p=0.085). CD44 expression on CTCs was not correlated with response to abiraterone. Array comparative genomic hybridization (aCGH) of CTC data has been performed in CTCs however the genomic data has been of an inconsistent nature due to multiple reasons discussed in the body of this report. Exploration of the immunocytochemistry, analysis of CTCs isolated on the Epic platform, and experiments to derive genomic data from these cells are underway. Phase I study of Abiraterone Acetate plus ARN-509 in men with mCRPC (UCSF PI: Friedlander) fully accrued, initial results showing PSA declines in men with treated with prior abiraterone and prior chemotherapy observed, indicating activity of this combination. Results presented at 2015 ASCO Annual Meeting and 2015 AACR annual meeting. Integration of both clinical trials with SU2C West Coast Dream Team castration-resistant prostate cancer biopsy protocol. Analysis of genomic data (RNAseq, whole exome sequencing) underway.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2015
- Accession Number
- ADA622720
Entities
People
- Terence W. Friedlander
Organizations
- University of California, San Francisco