ASPIRE-PC

A novel Androgen Synthesis Pathway in treatment-REsistant Prostate Cancer

Coordinatore	THE UNIVERSITY OF BIRMINGHAM    more  Organization address address: Edgbaston city: BIRMINGHAM postcode: B15 2TT contact info Titolo: Mr. Nome: Xavier Cognome: Rodde Email: send email Telefono: 441214000000 Fax: 441214000000
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	110˙803 €
EC contributo	110˙803 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-IEF
Funding Scheme	MC-IEF
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-03-01   -   2015-07-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE UNIVERSITY OF BIRMINGHAM  Organization address address: Edgbaston city: BIRMINGHAM postcode: B15 2TT contact info Titolo: Mr. Nome: Xavier Cognome: Rodde Email: send email Telefono: 441214000000 Fax: 441214000000	UK (BIRMINGHAM)	coordinator	110˙803.20

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 Obiettivo del progetto (Objective)

'Prostate cancer (PC) is the most prevalent non-cutaneous cancer in men and leads to high morbidity and mortality. Disseminated PC is treated by hormonal treatment in order to block intratumoral activation of the androgen receptor (AR) by 5α-dihydrotestosterone (DHT). Despite this treatment, eventually all patients develop castration-resistant disease (CRPC) which is accompanied by poor prognosis. Novel androgen synthesis and receptor inhibitors improve patient survival in CRPC, demonstrating the crucial role of residual androgen presence in PC despite castration. Besides the classic DHT synthesis pathway through testosterone, recent studies in humans have shown formation of DHT through an alternative pathway that does not require testosterone as an intermediate. Activity of this alternative androgen synthesis pathway is dependent on the presence of specific steroidogenic enzymes. Results of preliminary preclinical and clinical research show that levels of alternative pathway intermediates are increased in CRPC. Our goal is to investigate the activity and relevance of this novel pathway during progression of PC. The contribution of the alternative pathway to DHT-initiated AR activation will be explored using previously established in vitro models and sensitive steroid detection methods. This translational study will serve to discover novel targets for inhibition of intratumoral DHT synthesis and subsequent (CR)PC growth.'