NCI renews UCLA prostate SPORE grant

National Cancer Institute renews SPORE funding for 5-year cycle

UCLA's Jonsson Comprehensive Cancer Center and the department of urology at the David Geffen School of Medicine at UCLA have been notified that their standing as a National Cancer Institute Specialized Program of Research Excellence (SPORE) site in prostate cancer has been renewed for another five years.

The UCLA program is under the leadership of principal investigator Dr. Robert Reiter, Bing Professor of Urologic Research and a member of the Jonsson Cancer Center.

This renewal marks the beginning of a third five-year cycle of funding that will support UCLA scientists' efforts to improve the prevention, detection and treatment of prostate cancer. Thirty-thousand American men are expected to die from the disease this year, and the NCI estimates that more than 238,000 men will be diagnosed with prostate cancer in 2013.

The SPORE program is a central component of NCI's efforts to spur collaborative, interdisciplinary cancer research at academic centers throughout the U.S., with the goal of translating basic research from the laboratories into patient care more quickly and effectively. The five-year, $11.6 million grant will help UCLA expand its renowned prostate cancer program, which engages researchers and clinicians from many disciplines across campus to uncover the mysteries of the disease.

"The SPORE grant will robustly continue the outstanding programs we have developed over the last two cycles of the grant and give us the resources to bring investigators together for new innovative and multidisciplinary projects with the goal of improving the way we diagnose and treat prostate cancer," said Dr. Mark Litwin, professor and chair of UCLA's department of urology.

"This renewal of the UCLA prostate SPORE is indicative of the world-class research we have on this campus," said Dr. James Economou, UCLA vice chancellor for research and professor of microbiology, immunology and molecular genetics; molecular and medical pharmacology; and surgical oncology.

"The renewal of this SPORE grant is affirmation of the leadership role UCLA continues to play in groundbreaking research on prostate cancer," said Dr. Eugene Washington, vice chancellor for health sciences and dean of the Geffen School of Medicine.

"Over the past 10 years, the UCLA prostate SPORE has had some great successes," Reiter said. "Among them have been the development of the drug enzalutamide by Dr. Charles Sawyers and Dr. Michael Jung, the identification of prostate stem cells by Dr. Owen Witte and colleagues, and the discovery and development of antibodies against the prostate stem-cell antigen gene, which have all gone from discovery through to clinical trials. Other highlights include Dr. Hong Wu's work on the PTEN tumor suppressor gene, demonstrating that the gene negatively regulates prostate cancer stem cell self-renewal, proliferation and survival, and the work of Dr. Bill Aronson and colleagues demonstrating that dietary changes can affect the growth rate of prostate tumors."

According to the NCI, SPORE grants are designed to promote collaboration among the best scientific minds. The grants bring together researchers who might not otherwise have a chance to work together. The UCLA prostate SPORE is the only one in California and one of a handful in the U.S.

The specific aims of the renewed grant are:

• Conducting translational research to investigate what makes prostate cancer spread and become castration resistant, meaning that it does not respond to hormone therapy.

• Targeting cancer stem cells and signaling pathways.

• Evaluating the effects and mechanisms of dietary change in preventing prostate cancer.

• Providing organizational infrastructure and novel technologies to support SPORE objectives.

• Developing new research areas and supporting the careers of new researchers.

The SPORE grant will primarily fund four projects at UCLA:

• Dr. Robert Reiter and Dr. Anna Wu will focus on translating N-cadherin-targeted antibody therapy into the clinic. N-cadherin, a protein expressed widely across prostate cancers, is required for castration-resistant prostate cancer to emerge and survive, and it therefore is considered a credentialed target treatment for prostate cancer by the NCI.

• Dr. Hong Wu and Dr. Matthew Rettig will work to advance the management of castration-resistant prostate cancer by blocking the P13K and MAPK signaling pathways. An overarching hypothesis of this project is that prostate cancer can be classified according to alterations in signaling pathways - the mechanisms that underlie the formation of tumors. Individual tumors need to be classified according to which pathways are involved and must be treated with combination treatments that prevent an alternate pathway from being activated when one is blocked.

• Dr. Owen Witte, Dr. Matthew Rettig and Dr. Andrew Goldstein will be focusing on prostate cancer stem cells, which are thought to be resistant to castration and most conventional therapies. Their overall rational is that optimal cancer therapy requires targeting the bulk of differentiated or adult cancer cells as well as the cancer stem cells. This project will focus on targeting a gene called Trop-2, which is present on normal and malignant prostate stem cells. This is a novel approach to prostate cancer treatment.

• Dr. Bill Aronson and Dr. Pinchas Cohen will focus on the molecular effects of diet and how diet can help prevent and manage early prostate cancer. A previous study led by Aaronson and Cohen found that a low-fat diet supplemented with fish oil could slow the growth of prostate tumors.

Jonsson Cancer Center director Dr. Judith Gasson, a professor of medicine and senior associate dean for research, said that UCLA's prostate cancer program is a shining example of the campus's excellence in interdisciplinary research.

"We'll be able to move forward more quickly now to develop new and better ways to prevent, diagnose and treat prostate cancer with the goal of saving tens of thousands of lives every year," she said.

Source: University of California - Los Angeles