Embargoed until Dec. 21 at 2 p.m. PST
Kim Irwin, [email protected], (310) 206-2805
Kambra McConnel ([email protected]) (310) 206-3769
DISCOVERY AT UCLA'S JONSSON CANCER CENTER MAY LEAD TO NEW TREATMENTS FOR METASTATIC PROSTATE CANCER
New treatments for men with metastatic prostate cancer could develop from a discovery made by a research team at UCLA's Jonsson Cancer Center.
The treatments would involve shutting down a pathway that can carry excessive growth signals to prostate cells, thereby causing prostate cancer.
Dr. Charles Sawyers and his colleagues outline their research in tomorrow's (Dec. 22) edition of the journal Proceedings of the National Academy of Sciences.
Sawyers' group made its discovery almost simultaneously with related findings by several other scientists worldwide. However, Sawyers' work is the only research focusing on prostate cancer.
Sawyers and his team discovered that a specific gene called PTEN acts like a gate, opening and shutting access to the Akt pathway, which carries the growth-regulating signals.
Under normal conditions, PTEN keeps growth of cells in check so they don't divide inappropriately. But when it mutates, the PTEN gene breaks down and the gate won't close, causing too many growth signals to drive prostate cells to divide out of control, which can lead to cancer.
In previous laboratory experiments, Sawyers found that about half of men with metastatic prostate cancer have a mutated form of the PTEN gene.
"When PTEN is operating normally, it serves as a brake regulating cell growth," said Sawyers, who is director of the Prostate Cancer Program at UCLA's Jonsson Cancer -more- 2-2-2-2 RESEARCH MAY LEAD TO NEW DRUG
Center. "When the gene is mutated, the brake fails and the Akt pathway operates at runaway levels, promoting rapid cell growth always found in cancer."
Sawyers said the next step is for pharmaceutical companies to develop a new drug that can block the Akt pathway, thereby inhibiting prostate cancer growth in men with damaged PTEN genes.
Researchers at other institutions also are studying the Akt pathway. They have found it plays a role in other cancers besides prostate cancer, including brain and breast cancers, Sawyers said. Among those researchers are scientists at Columbia University, M.D. Anderson Cancer Center at the University of Texas, UC San Francisco and the University of Toronto.
Sawyers' work on the PTEN gene mutation and its relationship to the protein pathway sheds new light on prostate cancer, a disease that for years has frustrated scientists trying to target the killer of nearly 40,000 men every year.
"Prostate cancer has been a black box for years," Sawyers said. "Now we know there's a common genetic alteration in prostate cancer and we have proof of a pathway that regulates cell growth and is very amenable to drug development. This could be very good news for prostate cancer patients."
Also good news is the fact that scientists already know a lot about the Akt pathway, Sawyers said, allowing for development of a new drug to occur more quickly than usual.
"There already may be a drug in development that attacks this pathway," Sawyers said.
A new treatment for prostate cancer that attacks the Akt pathway would be the latest in targeted therapies, which determine what is broken in a cancer cell and attempt to fix it. Herceptin, a breast cancer drug developed in part at UCLA's Jonsson Cancer Center, works in the same way -- targeting a genetic mutation linked to cancer.
Developing a new drug that acts as a gate is a "very rationally designed therapy," Sawyers said.
The American Cancer Society estimates that more than 184,500 new cases of prostate cancer will be diagnosed in 1999. Every year, nearly 40,000 men die of prostate cancer, the most common non-skin cancer in American men. Nearly 80 percent of cases occur in men over 65.
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Sawyers said exciting work is being done in prostate cancer, particularly in the last two or three years.
"There is tremendous interest now in finding a way to fight this disease," he said.
Sawyers, who serves as associate chief for basic research and an associate professor in the Division of Hematology-Oncology at UCLA's Jonsson Cancer Center, recently received a Competitive Research Award from the Association for the Cure of Cancer of the Prostate (CaP CURE) to investigate new prostate cancer treatments that attack the Akt pathway. Sawyers also was named on Dec. 4 as the first winner of the Franklin D. Murphy Prize for his achievements in prostate cancer and leukemia research. The Murphy award is named for former UCLA Chancellor Franklin D. Murphy, who served from 1960 to 1968.
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For more information about UCLA's Jonsson Cancer Center, its people and resources, visit our site on the World Wide Web at http://www.cancer.mednet.ucla.edu.
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