PMID- 20524793
OWN - NLM
STAT- MEDLINE
DCOM- 20100910
LR  - 20240109
IS  - 1744-7658 (Electronic)
IS  - 1354-3784 (Linking)
VI  - 19
IP  - 7
DP  - 2010 Jul
TI  - New agents and strategies for the hormonal treatment of castration-resistant 
      prostate cancer.
PG  - 837-46
LID - 10.1517/13543784.2010.494178 [doi]
AB  - IMPORTANCE OF THE FIELD: Hormonal therapy with medical or surgical castration is 
      the mainstay of systemic therapy for advanced prostate cancer. Depletion of 
      gonadal testosterone in circulation is typically initially effective, although 
      responses are transient and metastatic disease progresses as castration-resistant 
      prostate cancer (CRPC). AREAS COVERED IN THIS REVIEW: CRPC is accompanied by a 
      gain of function in the androgen receptor (AR), which may occur at the level of 
      AR itself or through intratumoral repletion of androgens that in turn stimulate 
      AR. Investigational drugs in clinical trials have promising activity in CRPC. 
      Abiraterone acetate is a CYP17A1 inhibitor that blocks the synthesis of adrenal 
      androgens. MDV3100 is a nonsteroidal AR antagonist with a greater binding 
      affinity than other AR antagonists currently in clinical use. Insights into the 
      mechanisms of intratumoral steroidogenesis in CRPC have defined other potential 
      targets. Metabolism from DHEA to testosterone and dihydrotestosterone requires 
      3-hydroxyl oxidation and Delta(5) isomerization to Delta(4) by 
      3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17-keto reduction by 
      17beta-hydroxysteroid dehydrogenase (17betaHSD)-3 or -5. AR activation in CRPC by 
      intratumoral steroids requires these enzymatic steps. Investigation into specific 
      inhibitors of 3betaHSD and 17betaHSD are required to determine their efficacy and 
      potential roles in the treatment of CPRC. WHAT THE READER WILL GAIN: Readers will 
      gain an understanding of the biology of CRPC, new investigational hormonal agents 
      and novel approaches to the treatment of CRPC. TAKE HOME MESSAGE: Intratumoral 
      androgens drive CRPC progression. New investigational hormonal agents that 
      inhibit intratumoral androgens are highly active in the treatment of CRPC. 
      Alternative strategies hold the promise for the development of other agents with 
      novel mechanisms of action.
FAU - Sharifi, Nima
AU  - Sharifi N
AD  - Division of Hematology and Oncology, Department of Internal Medicine, University 
      of Texas Southwestern Medical Center, Dallas, TX 75390-8852, USA. 
      nima.sharifi@utsouthwestern.edu
LA  - eng
GR  - Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
PL  - England
TA  - Expert Opin Investig Drugs
JT  - Expert opinion on investigational drugs
JID - 9434197
RN  - 0 (AR protein, human)
RN  - 0 (Androgen Antagonists)
RN  - 0 (Androgen Receptor Antagonists)
RN  - 0 (Androgens)
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Receptors, Androgen)
SB  - IM
MH  - Androgen Antagonists/*therapeutic use
MH  - Androgen Receptor Antagonists
MH  - Androgens/*metabolism
MH  - Animals
MH  - Antineoplastic Agents, Hormonal/*therapeutic use
MH  - Clinical Trials as Topic
MH  - Drug Resistance, Neoplasm/drug effects
MH  - Humans
MH  - Male
MH  - Neoplasms, Hormone-Dependent/*drug therapy/metabolism
MH  - *Orchiectomy
MH  - Prostatic Neoplasms/*drug therapy/metabolism
MH  - Receptors, Androgen/metabolism
MH  - Treatment Outcome
RF  - 102
EDAT- 2010/06/08 06:00
MHDA- 2010/09/11 06:00
CRDT- 2010/06/08 06:00
PHST- 2010/06/08 06:00 [entrez]
PHST- 2010/06/08 06:00 [pubmed]
PHST- 2010/09/11 06:00 [medline]
AID - 10.1517/13543784.2010.494178 [doi]
PST - ppublish
SO  - Expert Opin Investig Drugs. 2010 Jul;19(7):837-46. doi: 
      10.1517/13543784.2010.494178.