Investigating IKBKE as a therapeutic target in castrate resistant prostate cancer (360G-Wellcome-207171_Z_17_Z)

Prostate cancer (PCa) is the most commonly diagnosed cancer affecting men with one in eight men developing the disease within their lifetime. Androgen receptor (AR) activation plays a critical role in PCa development and progression. Therapies which antagonise AR signalling are initially effective, however the majority of men relapse to develop an incurable form of PCa termed castrate-resistant PCa (CRPC) in which AR activation occurs independently of androgen stimulation. Consequently, there is an urgent need for the development of novel therapeutic strategies. The AR is not solely regulated by its cognate steroid hormone; it is also regulated by a variety of co-regulatory proteins, some of which are responsible for post-translationally modifying the AR. Interestingly, AR phosphorylation has been shown to be important in directly modulating AR activity. However, the protein kinases involved in AR activation in advanced and therapy resistant PCa remain ill defined. In a comprehensive siRNA kinome screen designed to identify kinases involved in the regulation of AR activity, the threonine/serine kinase, IKBKE, was identified as a putative AR activator. Therefore, subsequent evaluation of IKBKE signalling in PCa progression will be investigated. Specifically, this project will determine the effect of IKBKE inhibition on PCa cell growth and migration.