Androgen Metabolism in Progression to Androgen-Independent Prostate Cancer
Abstract
We have examined a series of prostate cancer xenografts to identify models that progress to castration resistant prostate cancer (CRPC) with reactivation of androgen receptor (AR) activity and increased expression of aldo-keto reductase family 1, member C3 (AKR1C3). Significantly, we found that tumor progression after castration in the VCaP xenograft is associated with reactivation of AR (including expression of the TMPRSS2-ERG fusion gene), and with an increase of ~5-fold in AKR1C3 gene expression. We are currently assessing whether inhibition of AKR1C3 will impair growth in this model. To assess androgen synthesis in patients progressing to CRPC, we have measured serum levels of androgen and metabolites and found that a subset have increased levels of the androgen metabolite 3alpha-diolG. We are currently assessing androgen levels in CRPC patients treated with agents to further suppress androgen synthesis to determine whether androgen levels correlate with responses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2008
- Accession Number
- ADA502868
Entities
People
- Steven P Balk
Organizations
- Beth Israel Deaconess Medical Center