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SUMMARY:Steroid Hormone Receptors in Prostate Cancer: A Hard Habit to Brea
 k? - Dr Gerhardt Attard\, The Institute of Cancer Research and the Royal M
 arsden Hospital
DTSTART:20091027T120000Z
DTEND:20091027T130000Z
UID:TALK19418@talks.cam.ac.uk
CONTACT:Mala Jayasundera
DESCRIPTION:The clinical data from abiraterone acetate and MDV-3100 confir
 m continued androgen receptor (AR) addiction in a significant proportion o
 f castration-resistant prostate cancers (CRPC). Abiraterone acetate is a h
 ighly specific inhibitor of CYP17 and results in significant suppression o
 f serum androgenic steroids and oestrogens1. Declines in PSA by ≥50% and
  ≥90% with abiraterone acetate have been reported in 50-60% and 20-30% o
 f CRPC patients respectively\, despite prior progression while castrate on
  several hormonal agents2. Importantly\, declines in PSA were associated w
 ith radiological tumour regression\, declines in circulating tumour cell (
 CTC) count and symptomatic benefit2. Moreover\, prior treatment with docet
 axel chemotherapy did not significantly alter sensitivity to abiraterone a
 cetate3. MDV-3100 is a potent AR antagonist which also induces tumour resp
 onses in CRPC patients4. Both these agents are now undergoing evaluation i
 n large\, randomized\, global\, phase III studies designed to identify a s
 urvival benefit and obtain regulatory approval to treat CRPC. However\, re
 sistance to these agents commonly develops within 18 months and is nearly 
 invariably characterized by a rising PSA\, suggesting resumption of transc
 ription of hormone-regulated genes. In fact\, although ETS gene fusions ap
 pear to be an early event in prostate carcinogenesis\, hormone-regulated o
 ver-expression of ERG persists in end-stage CRPC5. Also\, CRPC patients wi
 th a hormone-dependent ERG gene fusion are significantly more likely to ha
 ve a ≥90% PSA decline with abiraterone acetate5. The future development 
 of therapeutics for CRPC should be informed by the molecular classificatio
 n of CRPC using analytically validated predictive biomarkers in a combinat
 ion of tumour tissue and CTC and by a better understanding of the mechanis
 ms underlying disease progression following treatment with these novel\, h
 ormonal agents.\n\nReferences:\n\n1.	Attard G et al\, J Clin Oncol 26:4563
 -71\, 2008\n\n2.	Attard G et al\, J Clin Oncol\, 2009 XXX\n\n3.	Attard G e
 t al\, Cancer Res 69:4937-40\, 2009\n\n4.	Tran C et al\, Science\, 2009 XX
 X\n\n5.	Attard G et al\, Cancer Res 69:2912-8\, 2009\n\n\n\n\n\n
LOCATION:CRI Lecture Theatre
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