Journal
CURRENT OPINION IN ONCOLOGY
Volume 24, Issue 3, Pages 251-257Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCO.0b013e32835105b3
Keywords
androgen biosynthesis; androgen pathway-independent prostate cancer; androgen receptor; androgen receptor splice variants; castration-resistant prostate cancer; PTEN
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Funding
- Pacific Northwest Prostate Cancer SPORE [P50CA097186]
- DOD [PC093509, W81XWH-10-1-0133]
- Prostate Cancer Foundation
- [RC1 CA146849]
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Purpose of review The review highlights recently discovered mechanisms that sustain castration-resistant prostate cancer (CRPC) growth and describes advances in CRPC therapeutics. Recent findings Recent reports have shed new light on the molecular processes underlying CRPC survival during androgen deprivation therapy (ADT). This study summarizes recent findings and comments on their clinical relevance. Included in this review is a discussion on molecular mechanisms that regulate androgen receptor (AR) signaling in normal prostate epithelium and CRPC, biologically significant differences in the androgen-regulated transcriptional programs of androgen-dependent prostate cancer and CRPC, and recent discoveries involving de-novo androgen production and transport. We review the status and results of current clinical trials and finally, discuss the implications of evidence suggesting a declining importance of AR signaling in prostate cancers with PTEN loss. Summary Advances in the understanding of AR signaling in CRPC have identified novel drug targets and improved the rational design of targeted therapy, while illuminating a subset of prostate cancers that may progress to become completely independent of the AR signaling program.
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