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In mice, VN/124-1 + everolimus after bicalutamide


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Prolonging hormone sensitivity in prostate cancer xenografts through dual inhibition of AR and mTOR

Department of Pharmacology and Experimental Therapeutics, School of Medicine, University of Maryland, Health Science Facility I, Room 580G, 685 West Baltimore Street, Baltimore, MD 21201, USA.

To determine the mechanisms associated with loss of androgen dependency and disease progression in prostate cancer (PCa), we investigated the relationship between the androgen receptor (AR) and mTOR pathways and the impact of inhibiting both pathways in androgen-dependent and castration-resistant PCa models.

Androgen-dependent (LNCaP) and castration-resistant PCa (HP-LNCaP) cells were grown as tumours in SCID mice. Once tumours reached 500?mm(3), animals were grouped and injected subcutaneous with vehicle, our novel anti-androgen/androgen synthesis inhibitor, VN/124-1, bicalutamide, and everolimus. Tumour volumes were measured biweekly. The PSA and protein analyses were performed after completion of the treatment.

The addition of everolimus to bicalutamide treatment of resistant tumours significantly reduced tumour growth rates and tumour volumes. Anti-androgen treatment also increased protein expression of multiple signal transduction pathways earlier than vehicle-treated control xenografts. VN/124-1 plus everolimus acted in concert to reduce tumour growth rates in our castration-resistant xenograft model.

This study suggests that dual inhibition of AR and mTOR in castration-resistant xenograft models can restore sensitivity of tumours to anti-androgen therapy. Furthermore, after bicalutamide failure, dual inhibition with VN/124-1 and everolimus was the most effective treatment.

Written by:

Schayowitz A, Sabnis G, Goloubeva O, Njar VC, Brodie AM. [1]

Reference: Br J Cancer. 2010 Sep 28;103(7):1001-7.

doi: 10.1038/sj.bjc.6605882

PMID: 20842117 Forum: New agents Title: In mice, VN/124-1 + everolimus after bicalutamide

This extract can be found on http://PubMed.com, and is in the public domain.

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Any highlighting (except the title) is not by the author, but by Jim Marshall.

Jim is not a doctor.

This page was found on the Advanced Prostate Cancer Community for Australian men at http://advancedprost...lia.ipbhost.com.

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Click on the Contact Jim button at http://JimJimJimJim.com.

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