September 16, 2011
Penn Pharmacologist Receives Grant from Prostate Cancer Foundation to Find New Ways to Fight Drug Resistant Tumors
PHILADELPHIA —Trevor Penning, PhD, professor of Pharmacology at the Perelman School of Medicine at the University of Pennsylvania, and colleagues have received a 2011 Prostate Cancer Foundation Challenge Award. This is a multi-investigator grant awarded to Penn, Harvard University, University of Washington-Fred Hutchinson Cancer Center, and Beth Israel Deaconess Hospital to find new treatments for patients with advanced prostate cancer. The grant totals $500,000 per year for up to three years for all investigators.
Penning's role in the Prostate Cancer Foundation (PCF) award is two-fold. The first is to develop sophisticated assays to detect trace levels of male hormones called androgens in castrate-resistant prostate cancer (CRPC). CRPC is uniformly fatal and emerges because the tumor finds a way to make its own androgens. The new methods will allow the researchers to determine the source and fate of androgens within the disease, as well as mechanisms of drug resistance so that personalized therapies can be developed.
The second role is to develop inhibitors of a highly expressed protein (type 5 17beta-hydroxysteroid dehydrogenase) thought to be involved in the synthesis of androgens in CRPC within the prostate. Like other forms of prostate cancer, CRPC is androgen-dependent, but the tumor becomes aggressive by finding a way to by-pass castration by synthesizing its own hormones for growth.
“New therapies for CRPC target androgen synthesis, however, in many instances drug resistance can occur,” notes Penning. “The problem is that all patients are treated the same irrespective of how the tumor adapts to make its own androgens.” The research proposed will lead to tailored therapies for CRPC.
Abiraterone acetate (Zytiga), recently approved by the FDA for treatment for metastatic prostate cancer and soon to be approved within the European Union, is a new drug currently used after chemotherapy. As with previously approved treatments, patients invariably become resistant to abiraterone by mechanisms largely unknown. Overall, the team of researchers will investigate treatment-resistance mechanisms in abiraterone-resistant patients. Based on these findings, the team will design new androgen receptor pathway-targeted medications that should result in durable cancer remission.
"PCF Challenge Awards support transformational prostate cancer research teams to accelerate progress towards the reduction of death and suffering due to recurrent or advanced prostate cancer," comments Howard R. Soule, PhD, PCF chief science officer. "This multi-institutional research program will significantly advance our knowledge of why some men become resistant to treatment with abiraterone and identify new targets and treatments for them."
The PCF Challenge Awards will support a total of 10 scientific projects nationwide.
Co-investigators are Peter Nelson, MD; Glenn Bubley, MD; Toni Choueiri, MD; Phillip Kantoff, MD; Christopher Sweeney, MD; Mary-Ellen Taplin, MD; Steven Plymate, MD; Robert B. Montgomery, MD; Robert Vessella, PhD; Lawrence True, MD; Alvin Matsumoto, MD; Elahe Mostaghel, MD, PhD
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