Androgen Receptor Genomic and Splicing Alterations in Prostate Cancer
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 receptor transcription factor important for normal prostate function as well as the growth of prostate cancer. Because of the central importance of the AR in prostate cancer, the mainstay treatment for relapsed or metastatic disease is androgen depletion. The primary limitation of androgen depletion is that prostate cancer will eventually develop therapy resistance and recur with a lethal androgen depletion-independent phenotype. A wealth of clinical and experimental evidence has demonstrated that the AR is aberrantly re-activated at this stage of the disease and therefore remains a viable therapeutic target. This laboratory employs molecular, biochemical, cell biology, and genetic approaches to understand the mechanisms of AR has identified alternative mechanisms of AR activation that are impervious to current modes of androgen depletion, and are studying whether these mechanisms of AR activation can be exploited to develop novel targeted therapies for advanced prostate cancer. MSI resources are used to interrogate alterations in the sequence and structure of the AR gene, and understand the impact of these changes on AR mRNA expression, the AR cistrome, and the AR transcriptome in prostate cancer cell lines and tissues.
A bibliography of this group’s publications is attached. A Research Spotlight about this project appeared on the MSI website in January 2014.
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