Androgen Receptor (AR) Activity in Castration-Resistant Prostate Cancer (CRPC) and Response to Ketoconazole
- To determine whether pre-treatment androgen receptor (AR) activity correlates with
progression-free survival (PFS) of men with castration-resistant prostate cancer (CRPC)
treated with ketoconazole.
- To determine whether expression of androgen transport/synthesis/metabolism genes
(including CYP17A1, AKR1C3, HSD3B2, HSD17B3, HSD17B6, AKR1C2, AKR1C1, UGTB15, UGTB17,
SRD5A1, SRD5A2, SRD5A3, and SLCO2B1) correlate with detected AR activity, time to
progression, and overall survival (OS) following treatment with ketoconazole.
- To determine whether semi-quantitative immunohistochemical analysis of AR and AKR1C3
protein levels correlate with PFS following treatment with ketoconazole.
- To determine whether specific AR splice variations correlate with PFS in response to
- To determine whether detected activity of signaling pathways that interact with AR
pathway activity (e.g., PI3K and downstream effectors, SRC, others) correlate with
detected AR activity, PFS, and OS.
- To determine whether AR gene amplification correlates with detected AR activity and PFS
- To determine whether levels of testosterone and dihydrotestosterone from tumor tissue
correlate with AR activity and PFS on ketoconazole.
- To determine the presence of specific prostate cancer-associated gene translocations in
each sample of CRPC.
- To provide an unbiased data set of gene expression in CRPC that will markedly expand
the currently available public domain data.
- To provide a library of amplified RNA and cDNA for further analysis by other
OUTLINE: This is a multicenter study.
Archived bone marrow tissue and blood samples are analyzed for androgen receptor (AR), AR
splice variations, expression of androgen transport/synthesis/metabolism genes, AKR1C3
protein levels, and testosterone and dihydrotestosterone levels by RT-PCR, SNP microarrays,
IHC, gene expression analysis, and mass spectrometry methods.
Progression-free survival (PFS) of men treated with ketoconazole
Mary-Ellen Taplin, MD
Dana-Farber Cancer Institute