SAN FRANCISCO, CA USA (UroToday.com) - Dr. Peter Nelson opened the 2014 GU Cancers Symposium meeting by highlighting some new findings regarding the role of androgen receptor (AR) in prostate cancer.
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He reviewed some recent findings showing that androgen-AR interactions mediate genotoxic stress, in addition to more canonical AR-mediated transcriptional programs.
Two studies published in the last 5 years have shown that androgen-AR interactions actually induce intranuclear proximity of genomic loci which facilitates creation of recurrent genetic rearrangements that are seen clinically -- such as those involving the TMPRSS2-ERG translocations. Not only do androgen-AR interactions juxtapose these genomic loci, but they also recruit enzymes which mediate double-strand DNA breaks (DSBs) and error-prone DNA repair. This process results in TMPRSS2 translocations.
Dr. Nelson also nicely laid the framework for other speakers by reviewing androgen and AR dependence in the natural history of prostate cancer. He pointed out that there are 4 states which define the AR program: endocrine androgen activation of AR, intracrine androgen activation of AR, ligand-dependent but still AR-dependent, and finally AR-indepenent. The highlight of the talk was his outline of reasons for the prostate cancer community to be both optimistic and pessimistic about curing prostate cancer using AR-based therapies.
Highlights of a presentation by Peter Nelson, MD at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
Fred Hutchinson Cancer Research Center, Seattle, WA USA