The designation as a Specialized Program of Research Excellence (SPORE) comes with a five-year, $11.5 million grant to further expand UCLA’s renowned prostate cancer program, pulling in researchers and clinicians from a variety of disciplines to work together to uncover the mysteries of prostate cancer.
The SPORE is the second for UCLA’s Jonsson Cancer Center. In April 2001, the lung cancer program was designated a center of research excellence, receiving a $13.9 million grant from the National Cancer Institute.
“This prostate cancer SPORE gives us the resources and the opportunity to pull together multiple investigators to work toward the goal of improving the way we diagnose and treat prostate cancer,” said Dr. Jean deKernion, chairman of the UCLA Department of Urology and the Clark Urology Center and director of the new prostate cancer SPORE. “We’ve been building an outstanding prostate cancer program for the last five to seven years, and that program will provide an excellent foundation for this center of research excellence.”
The SPORE will focus on two major areas, deKernion said. Researchers will seek to identify new molecular targets for therapies — attempting to fix what’s broken in the prostate cancer cell — and investigate nutritional strategies to prevent the disease and impede tumor growth.
“We believe nutrition will play a critical role in the future in preventing prostate cancer,” said Dr. William Aronson, an associate clinical professor of urology, a Jonsson Cancer Center researcher and one of the investigators heading up the nutrition study.
“Nutrition also may play a role, either alone or combined with other treatments, for patients with existing prostate cancer.”
SPORE grants are designed to promote collaboration among the best scientific minds, National Cancer Institute officials said. The grants bring together researchers who might not otherwise have a chance to work together on their far-flung academic campuses and in their large medical institutions, deKernion said. The goal is to translate basic research from the laboratories into patient care much more quickly and effectively. UCLA’s SPORE will bring together scientists specializing in cell signaling, gene expression, pathology, molecular imaging, epidemiology, biostatistics, immunology and biological chemistry to share their theories as well as their research findings.
“We’re bringing together the best of our laboratory scientists and clinical researchers to move the most promising concepts forward for clinical evaluation in patients with prostate cancer,” deKernion said.
The timing of the grant is optimal: “Awareness about prostate cancer is increasing. Scientifically, we’re at the point now where we can make significant advances in prevention, detection and treatment,” deKernion said.
UCLA’s Jonsson Cancer Center is the only prostate cancer SPORE in Southern California, and one of only nine in the United States.
This year alone, an estimated 189,000 American men will be diagnosed with prostate cancer, according to the American Cancer Society.
Five key projects form the core of the UCLA SPORE, most of which have their scientific roots in Jonsson Cancer Center labs. Four of the projects focus on cell-surface antigens and cell-signaling pathways implicated in prostate cancer. The goal is to develop targeted therapies that focus on what is broken in the cancer cell. The fifth project will explore the relationship between diet and prostate cancer.
The SPORE projects include:
· Drs. Robert Reiter and Owen Witte will focus on PSCA, or prostate stem cell antigen, which sits on the surface of prostate cancer cells in about 80 percent of men with the disease. The study will evaluate the role of PSCA in the cause and progression of prostate cancer and examine the effects of antibody therapy targeting PSCA. The study ultimately will lead to clinical trials using a monoclonal antibody against PSCA in men with high-risk prostate cancer. In laboratory models, the antibody — generated in Reiter’s UCLA laboratory — has exhibited anti-tumor activity.
· Drs. Charles Sawyers, Reiter and Diane Prager will test the drug rapamycin on a group of men whose prostate cancer cells lack PTEN, a gene that acts like a switch regulating access to a cell-signaling pathway. UCLA researchers have discovered that cells lacking PTEN are more sensitive to rapamycin. About 20 percent of men with prostate cancer lack the PTEN gene. The study also seeks to develop and optimize techniques to determine the status of the PTEN gene in patients through prostate biopsies.
· Drs. Pinchas Cohen and Peter Tontonoz will study the potential interactions of two key cell-signaling pathways found to be important in prostate cancer development. The first involves growth factors known as insulin-like growth factors (IGFs) and their binding proteins (IGFBPs), recently recognized as critical regulators of prostate cancer development. The second is a family of retinoid receptors that include the retinoid X receptor (RXR) and the peroxisome proliferator activated receptor (PPAR). Evidence derived in UCLA labs indicates that the IGFBP and RXR pathways interact and synergize in inducing prostate cancer cell death. The researchers will attempt to use retinoids and IGFBPs to induce prostate cancer cell death, first in laboratory models and later in humans. Their goal is to develop less toxic, more effective treatments for men with advanced prostate cancer.
· Drs. David Agus and Phillip Koeffler will focus on developing targeted therapies that inhibit the growth of prostate cancer. Their laboratory studies currently are evaluating the effectiveness of drugs that target and turn off a key growth-signaling pathway called the epidermal growth factor receptor (EGFR). The EGFR is a part of the HER kinase family of proteins that regulate cell growth and can stimulate the spread of tumors when over-expressed on cancer cells. Ultimately, these studies will lead to an understanding of the molecular mechanisms involved in the growth and treatment of prostate cancer. Other studies in the laboratory and in clinical trials will examine the effectiveness of using a monoclonal antibody to target a protein called HER-2/neu that controls cell growth. · Drs. Aronson, Cohen, John Glaspy and nutritionist and researcher Dilprit Bagga will investigate whether a low-fat diet with fish-oil supplements can be used to prevent and/or treat prostate cancer. Researchers believe the type of dietary fat is likely to be important in prostate cancer development, and their strategy calls for a decrease in omega-6 fatty acids found in animal and vegetable fats and an increase in omega-3 fatty acids delivered through dietary fish and fish-oil supplements. Laboratory studies at UCLA have shown that a low-fat diet and omega-3 fatty acids inhibit the growth of prostate cancer cells in test tubes and in animal models. Human studies will focus on men with prostate cancer and will determine if and how this diet works to prevent or treat the disease.
“There are a lot of reasons to think that the risk for prostate cancer can be lowered through diet,” said Glaspy, who also has studied a low-fat diet with fish-oil supplements in women with breast cancer. “Men in Japan, where they eat more omega-3 fatty acids, have a much lower incidence of prostate cancer than men in American, where we consume more omega-6 fatty acids. That can’t be a coincidence.”
Sawyers, who has been investigating prostate cancer for nearly a decade, said the five core UCLA SPORE projects represent a well-rounded attack against the disease.
“We’re covering the major signaling pathways that we think are involved in prostate cancer,” he said. “UCLA has invested in basic science programs that are bearing fruit now and have clinical implications. This is an opportunity to put these ideas into clinical trials.”
Dr. Judith C. Gasson, Jonsson Cancer Center director and a professor of medicine and biological chemistry, said the prostate cancer SPORE is evidence of the excellence in interdisciplinary research at UCLA.
“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,” Gasson said.
For more information about UCLA’s Jonsson Cancer Center, its people and resources, visit our site on the World Wide Web at www.cancer.mednet.ucla.edu/.