Androgen Metabolism in Progression to Androgen-Independent Prostate Cancer
Abstract
We have proposed that prostate cancers adapt to androgen deprivation therapy by increasing their synthesis of potent androgens from available weak adrenal androgens (and possibly from endogenous precursors), and that AKR1C3 is a key enzyme in this process. Our objectives are to test these hypotheses using cell line and xenograft models (Aim 1) and by measuring androgen and androgen metabolite levels in patients who progress to CRPC (Aim 2). The progress reported here strongly supports the conclusion that a mechanism for tumor progression after androgen deprivation is increased intratumoral androgen synthesis. Further xenograft studies will focus on the VCaP model using additional drugs and shRNA approaches to inhibit key enzymes in androgen synthesis. Studies in clinical material will focus on the analysis of additional samples, and on correlating effects on androgen levels with clinical responses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2009
- Accession Number
- ADA552661
Entities
People
- Steven P Balk
Organizations
- Beth Israel Deaconess Medical Center