Journal
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
Volume 27, Issue 3, Pages 251-257Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.urolonc.2009.03.016
Keywords
Prostate cancer; Hormone therapy; Castration resistant; Metastatic; Androgen metabolism; Intracrinology; Steroidogenesis
Categories
Funding
- NCI NIH HHS [5K23 CA122820-02, K23 CA122820, P50CA97186, P50 CA097186, P50 CA097186-07, K23 CA122820-03] Funding Source: Medline
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Emerging evidence Suggests that despite testicular androgen ablation. residual androgens, likely of adrenal-though potentially of prostatic-origin, play a critical role in the progression of prostate cancer to recurrent castration-resistant disease. Thus. a reassessment of the concept of total androgen deprivation is warranted. Current treatment strategies may not only lack optimal efficacy, but may actually contribute to the selection of neoplastic clones adapted to exist and proliferate in a low (but not zero) androgen environment. Moreover. the 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. Recent Studies by Our group and others indicate that prostate cancers undergo all adaptive response to castration that is associated with the up-regulation of transcripts encoding enzymes involved in the biosynthesis of androgens. Targeting these metabolic enzymes either individually or using combinations of agents to inhibit testicular, adrenal, and intracrine sources may provide enhanced clinical responses in the setting of both localized and metastatic disease. (C) 2009 Elsevier Inc. All rights reserved.
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