Effects of Sorafenib on <em>C</em>-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells

• Main Authors: Mark Schrader, Bianca Nitzsche, Michael Höpfner, Marcus V. Cronauer, Andres J. Schrader, Friedemann Zengerling, Wolfgang Streicher
• Format: Article
• Language: English
• Published: MDPI AG 2012-09-01
• Series: International Journal of Molecular Sciences
• Subjects: sorafenib; truncated androgen receptor variants; castration resistant prostate cancer
• Online Access: http://www.mdpi.com/1422-0067/13/9/11530

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, <em>C</em>-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.