期刊
BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM
卷 22, 期 2, 页码 243-258出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.beem.2008.01.003
关键词
prostate cancer; hormone therapy; castration resistant; metastatic; androgen metabolism; intracrinology; steroidogenesis
资金
- NCI NIH HHS [5 K23 CA 122820-02, K23 CA122820, K23 CA122820-01, P50 CA 97186, P50 CA097186] Funding Source: Medline
Residual tissue androgens are consistently detected within the prostate tumors of castrate individuals and are thought to play a critical role in facilitating the androgen receptor-mediated signaling pathways leading to disease progression. The source of residual tumor androgens is attributed in part to the uptake and conversion of circulating adrenal androgens. Whether the de novo biosynthesis of androgens from cholesterol or earlier precursors occurs within prostatic tumors is not known, but it has significant implications for treatment strategies targeting sources of androgens exogenous to the prostate versus 'intracrine' sources within the prostatic tumor. Moreover, increased expression of androgen-metabolizing genes within castration-resistant metastases suggests that up-regulated activity of endogenous steroidogenic pathways may contribute to the outgrowth of 'castration-adapted' tumors. These observations suggest that a multi-targeted treatment approach designed to simultaneously ablate testicular, adrenal and intracrine contributions to the tumor androgen signaling axis will be required to achieve optimal therapeutic efficacy.
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