WASHINGTON, DC USA (UroToday.com) - Options for CRPC include chemotherapy, immune therapies and androgen inhibitors. Also, bone targeted agents can decrease skeletal related events. Microtubule drugs, such as taxanes block microtubules that engage AR in growth signaling interactions. Androgens regulate cytoskeletal reorganization and AR overexpression and reverse androgen induced cytoskeleton reorganization in PC-3 cells. Androgens and TGF-B independently promote EMT in prostate cancer cells. Thus, Dr. Kyprianou was interested in linking the androgen axis with taxanes in prostate cancer. Steroids regulate tubulin post-translation modification and decrease microtubule density. Docetaxel inhibits PSA expression in human prostate tumors. She showed data that microtubule-targeting drugs inhibit AR transcriptional activity. They also inhibited ligand independent activation of AR, as shown via the EGF pathway. Docetaxel decreased nuclear translocation of AR in human specimens. Tubulin binding to AR engages the N-terminal domain and this is inhibited by taxanes. The addition of an AR-binding moiety to Taxol structures may target AR-expressing prostate cancer cells to further increase therapeutic efficacy.
Presented by Natasha Kyprianou, MD, PhD at the Society for Basic Urologic Research (SBUR)/Society of Urologic Oncology (SUO) joint meeting during the American Urological Association (AUA) Annual Meeting - May 14 - 19, 2011 - Walter E. Washington Convention Center, Washington, DC USA
Reported for UroToday by Christopher P. Evans, MD, FACS, Professor and Chairman, Department of Urology, University of California, Davis, School of Medicine.
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