ASCO GU 2008 - Correlating Androgen Levels And Steroidogenic Enzyme Expression In Castration-Resistant Prostate Cancer (CRPC) Metastases

Main Category: Prostate / Prostate Cancer
Also Included In: Endocrinology;  Urology / Nephrology
Article Date: 16 Feb 2008 - 1:00 PDT

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UroToday.com - Dr. Mostaghel reviewed the potential sources of tissue androgens from the androgen metabolic pathway. This includes the uptake and conversion of circulating adrenal androgens, and the de novo androgen biosynthesis of androgens from cholesterol, progesterone or earlier precursors.

Tumor tissue was obtained from the warm autopsy study at the University of Washington. Testosterone levels within castration resistant metastases were measured and are significantly elevated compared to primary prostate tissues in these autopsy samples. Expression of steroidogenic transcripts in CRPC metastases is greater than primary tumors. SQLE and LSS are 2 genes involved early in the cholesterol synthesis process that were elevated in these samples. Also increased cholesterol membrane translocation and metabolism genes were altered. A correlation between androgen levels and transcript expression in CRPC metastases was made. Groups of genes that correlated with DHT or testosterone in CRPC metastasis were found. They were fitted into the synthesis pathways to correlate with mechanism and thus may represent targets. The simultaneous targeting of multiple enzymes comprising the intracrine steroidogenic pathway may thus provide clinical utility.

Presented by E. A. Mostaghel at the American Society of Clinical Oncology (ASCO) - 2008 Genitourinary Cancers Symposium - A Multidisciplinary Approach - February 14-16, 2008 San Francisco, California, USA

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS Professor & Chairman Department of Urology University of California, Davis, School of Medicine Sacramento, CA

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