Research in the Dehm laboratory focuses on the role of the androgen receptor (AR) in prostate cancer development and progression. The AR is a steroid hormone transcription factor that is regulated by the physiologic androgens testosterone and dihydrotestosterone. In prostate cells (both normal and cancerous) AR functions as a master-regulator transcription factor. Treatments for metastatic prostate cancer depend on blocking the production or action of these androgens to inhibit the growth- and survival-promoting functions of the AR. Androgen depletion is therefore one of the earliest examples of targeted cancer therapy. The primary limitation of androgen depletion is that prostate cancer will eventually develop resistance and recur with a lethal castration-resistant phenotype. Resistance and disease recurrence is frequently due to re-activation of the transcriptional activation functions of the AR, but can also occur via AR bypass mechanisms. This laboratory is employing genomics approaches such as DNA-seq, RNA-seq and ChIP-seq to understand the changes that occur in the target (the AR) in response to the targeted therapy (androgen depletion). Their ultimate goal is to exploit their findings to develop new AR-targeted therapies that could more effectively and durably suppress prostate cancer growth.
This research was featured on the MSI website in January 2014: Fighting Prostate Cancer.