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Castration-resistant prostate cancer: Targeting androgen metabolic pathways in recurrent disease
Urologic Oncology: Seminars and Original Investigations, 07/01/09

Mostaghel EA et al. - In a review of androgen metabolic pathways in recurrent castration-resistant prostate cancer (PC), targeting these metabolic enzymes either individually or using combinations of agents to inhibit testicular, adrenal, and intracrine sources may provide enhanced clinical responses in both localized and metastatic disease.

Methods

Evidence suggests that despite testicular androgen ablation, residual androgens, likely of adrenal—though potentially of prostatic—origin, play a critical role in progression of PC to recurrent castration-resistant disease.
Reassessment of the concept of total androgen deprivation is warranted.
Current treatment strategies may not only lack optimal efficacy, but may actually contribute to selection of neoplastic clones adapted to exist and proliferate in a low (but not zero) androgen environment.
Adequacy of androgen receptor (AR) pathway inhibition cannot be surmised from serum or plasma androgen levels, but must be ascertained at the tissue and molecular level prior to drawing conclusions regarding clinical efficacy or failure.

Results

Recent studies indicate that PCs undergo an adaptive response to castration that is associated with the up-regulation of transcripts encoding enzymes involved in the biosynthesis of androgens.

Risk of dying from prostate cancer in men randomized to screening
Cancer, 10/13/09 Relevance Score: 72%

Prostate Cancer Specific Mortality and Gleason 7 Disease Differences in Prostate Cancer Outcomes Between Cases With Gleason 4 + 3 and Gleason 3 + 4 Tumors in a Population Based Cohort
The Journal of Urology, 11/20/09 Relevance Score: 71%

A prospective study of lifetime physical activity and prostate cancer incidence and mortality
British Journal of Cancer, 11/02/09 Relevance Score: 71%

Association of 17 prostate cancer susceptibility loci with prostate cancer risk in Chinese men
The Prostate, 11/02/09 Relevance Score: 71%

Prostate specific antigen for early detection of prostate cancer: longitudinal study
British Medical Journal, 10/08/09 Relevance Score: 71%