Recent evidence suggests that the development of castration resistant prostate cancer (CRPCa) is commonly associated with an aberrant, ligand-independent activation of the androgen receptor (AR).
A putative mechanism allowing prostate cancer (PCa) cells to grow under low levels of androgens, is the expression of constitutively active, C-terminally truncated AR lacking the AR-ligand binding domain (LBD). Due to the absence of a LBD, these receptors, termed ARΔLBD, are unable to respond to any form of anti-hormonal therapies. In this study we demonstrate that the multikinase inhibitor sorafenib inhibits AR as well as ARΔLBD-signalling in CRPCa cells. This inhibition was paralleled by proteasomal degradation of the AR- and ARΔLBD-molecules. In line with these observations, maximal antiproliferative effects of sorafenib were achieved in AR and ARΔLBD-positive PCa cells. The present findings warrant further investigations on sorafenib as an option for the treatment of advanced AR-positive PCa.
Written by:
Zengerling F, Streicher W, Schrader AJ, Schrader M, Nitzsche B, Cronauer MV, Höpfner M. Are you the author?
Department of Urology, Ulm University, Ulm 89075, Germany. ; ; ; Department of Physiology, Charité Universitätsmedizin, Campus Benjamin Franklin, Berlin 14195, Germany. ;
Reference: Int J Mol Sci. 2012;13(9):11530-42.
doi: 10.3390/ijms130911530
PubMed Abstract
PMID: 23109869
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