Researchers at UCLAâ€™s Jonsson Cancer Center and in the Department of Urology have demonstrated for the first time that they can locate difficult-to-detect prostate cancer metastases in laboratory models, a discovery that could lead to safer and more effective gene-based treatments for advanced prostate cancer.
UCLA researchers engineered a virus that can identify prostate cancer cells based on the prostate-specific antigen (PSA) protein expressed only in prostate cells. Using the substance that makes fireflies glow, scientists showed through high-tech imaging that the prostate-targeted virus made prostate cancer cells appear as â€œhot spots,â€? both in primary tumors and in distant metastases that were still too small to cause symptoms or appear on conventional detection scans. The next step, researchers say, will be to attach gene-based therapies to the virus, which would act as a vehicle to deliver the toxic treatment directly to the prostate cancer cells and, it is hoped, kill them.
The discovery is outlined in the Aug. 1 issue of the peer-reviewed journal Nature Medicine. The journal article was selected for early online publication and will be featured July 22 on www.nature.com.
â€œProstate cancer metastases are difficult to detect and hard to treat,â€? said Lily Wu, lead author of the article, a Jonsson Cancer Center researcher and an assistant professor of urology and pediatrics. â€œWith this method, weâ€™ve shown we can deliver a targeted virus into a lab model and can demonstrate that it is expressed only in prostate cancer cells. That means we can also deliver a targeted therapy to prostate cancer cells. The idea would be to deliver a toxic gene to the cancer that would not harm surrounding healthy cells.â€?
Wu, who also is a member of the Crump Institute for Molecular Imaging, estimates the gene-based delivery system could be tested in humans within three to five years.
Doctors administering gene therapy now have no way to determine quickly that it reaches the cancer cells itâ€™s targeting. Doctors and patients are forced to wait weeks or months for any positive response to treatment that may indicate the therapy is attacking the cancer.
This discovery, however, could allow doctors to monitor the progress of gene therapy in the human body almost immediately, not only in primary tumors but in distant organs that may be at risk as well.
The Nature Medicine article states that â€œrepetitive imaging over a three-week period after injection into tumor-bearing mice revealed that the virus could locate and illuminate metastases in the lung and spineâ€? of laboratory models.
Dr. Kenneth J. Pienta, director of Urologic Oncology at the University of Michigan Medical Center, said Wuâ€™s research is important because it â€œrepresents a novel and unique way to image prostate cancer cells as they move through the body and grow in various places.â€?
â€œAlthough we are only able to do this in animals now, it is only a matter of time before we can do this in people,â€? said Pienta, who also is a professor of medicine and urology. â€œThis discovery allows us to more rapidly assess how cancers that are growing in animals respond to various treatments, and, ultimately, will allow for the more rapid development of therapies to treat advanced prostate cancer.â€?
Harvey Herschman, director of basic research at UCLAâ€™s Jonsson Cancer Center, likened Wuâ€™s discovery to a tumor-specific searchlight and said it will have â€œtremendous importanceâ€? if it can be translated into humans.
â€œOne of our problems is that we donâ€™t have a way to find very small metastases in people,â€? Herschman said. â€œPatients may be carrying small tumors and we may not know it. If we knew they had these small metastases and where they were located, we could treat them when theyâ€™re still too small to cause any symptoms or show on scans.â€?
The current method and further amplification of the imaging signals that Wu and her colleagues are working on could theoretically find such tiny cancer spreads in patients much earlier than is possible now, and allow doctors to treat these metastases sooner, when the chances of success are greater.
â€œThis targeted gene delivery method will help us to catch a metastasis when it is still a small group of cells, instead of a tumor on the spine or in the lung,â€? Wu said. â€œThis could make any kind of gene therapy much safer, and we wouldnâ€™t be doing it blindly. Weâ€™d be able to see that the toxin is getting delivered to the right place.â€?
Prostate cancer is the second leading cause of cancer deaths in American men. This year, about 189,000 new cases of prostate cancer will be diagnosed and more than 30,000 American men will die, according to the American Cancer Society. Although men of any age can get prostate cancer, it is found most often in men over 50.
Wuâ€™s discovery was based on a very basic concept â€” restricting the expression of a gene only in PSA-producing prostate cancer cells â€” coupled with technological advances that allowed her and her team to develop the vehicle and track it with a special camera able to pick up and display the firefly luminescence.
Although the camera detected the â€œhot spotsâ€? in animal models, it will not be able to do the same in humans, Wu said. A different imaging system will be needed, and other UCLA researchers are working on such a system now using positron emission tomography, or PET scanning.
In January 2001, the National Cancer Institute awarded Jonsson Cancer Center researchers a $9.8 million grant, under the leadership of Herschman, to establish a new molecular imaging center that will develop innovative ways to see gene-based therapies at work in the human body. Research at the imaging center is expected to shed new light on the safety and effectiveness of gene therapy and other gene-based treatments. Investigations also may provide important clues about how cancer develops, grows, spreads, forms its own blood supply for nourishment and interacts with the human immune system.
For more information about UCLAâ€™s Jonsson Cancer Center, its people and resources, visit our website: www.cancer.mednet.ucla.edu .