The prostate cancer program at the UCLA Jonsson Comprehensive Cancer Center and UCLA Health has been awarded an $8.7 million Specialized Program of Research Excellence, or SPORE, grant from the National Cancer Institute. The grant will support the development of new and innovative approaches for improving the diagnosis, prognosis and treatment of prostate cancer.
The 2019 designation recognizes UCLA's prostate cancer program as one of the best in the country and marks the fourth time it will be receiving the five-year cycle of funding. The program is one of only eight current such programs and the only one to be awarded the designation in the state of California.
"For the past 15 years, the SPORE grant has played a pivotal role in bringing a sense of cohesiveness to our program," said principal investigator of the grant Dr. Robert Reiter, professor of urology and director of the UCLA Prostate Cancer Program. "It funds projects that include researchers and scientists from diverse disciplines and backgrounds all around campus — such as chemistry, nanotechnology, radiology, pathology and stem cell biology — to help accelerate our goal of combating prostate cancer."
Under the leadership of Reiter, the grant has helped lead to significant discoveries that have had a major impact on how men with prostate cancer are treated. Most notably, the grant helped support the work of Dr. Michael Jung, a UCLA distinguished professor of chemistry and biochemistry, and Dr. Charles Sawyers, a former professor of medicine and molecular pharmacology at UCLA. They worked to develop the drugs enzalutamide and apalutamide, anti-androgen (testosterone blocker) treatments that can prolong life for men who have failed hormone and chemotherapies. These drugs have been used by thousands of men with castration-resistant prostate cancer.
Developments in imaging for detecting prostate cancer have also been supported through the grant. UCLA was among the first places in the country to employ MRI for detection, diagnosis and management of prostate cancer. Now, MRIs are used regularly to detect and assess the aggressiveness of malignant prostate tumors.
Among American men, prostate cancer is the most common cancer diagnosis and the second leading cause of cancer-related death. In 2018 there were an estimated 164,690 new cases of prostate cancer and 29,430 deaths from this disease reported in the United States.
Over the next five years, the grant will fund three translational research projects to find better ways to treat men with advanced stages of the disease:
- Developing drug inhibitors for men with metastatic castration-resistant prostate cancer. Led by Jung and Dr. Matthew Rettig, the team will look to develop a drug inhibitor that targets the androgen receptor N-terminal domain to help with various tumor escape mechanisms from current androgen receptor-targeted therapies. Researchers are hoping the inhibitor will help minimize resistance, prolong the life expectancy and improve the quality of life for men with metastatic castration-resistant prostate cancer. This stage of prostate cancer accounts for virtually all prostate cancer-specific deaths.
- Using CAR T-cell therapy to treat men with advanced prostate cancer. Working with researchers at City of Hope, Dr. Owen Witte and colleagues will be testing a new CAR T-cell targeting the prostate stem cell antigen in prostate cancer. The team has engineered and tested the CAR T-cell therapy in laboratory models of prostate cancer and will now be bringing them to a human clinical trial to test its efficiency.
- Targeting a protein to help inhibit lethal prostate cancer. The project, led by Dr. Isla Garraway from UCLA and Michael Freeman from Cedars Sinai, will test if the protein ONECUT2 is a target in a subset of aggressive prostate cancers where ONECUT2 is highly active. Currently, most drugs being developed to treat advanced prostate cancer are primarily focused on targeting the androgen receptor, which many men still do not benefit from. Jung and his medicinal chemistry team are also involved in this project.
"This technology being funded has the potential to transform the treatment of prostate cancer," said Dr. Michael Teitell, director of the Jonsson Cancer Center. "The support from the SPORE grant makes it possible for our researchers and physicians to bring observations from the clinic into the lab, to better understand why some patients respond, why some don't, and to really understand it at the scientific level so they can develop new drugs and tools to overcome the obstacles that currently exist."