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UCLA Jonsson Cancer Center Researchers Study Ways to Prevent Tobacco-Related Bladder Cancer

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$5.9 million National Cancer Institute grant to fund large clinical trial

testing green-tea extract, Iressa as cancer-prevention agents

Scientists and physicians at UCLA’s Jonsson Cancer Center are launching on Aug. 28 a first-of-its-kind, comprehensive program to prevent smoking-related bladder cancer.

As part of the program, researchers will develop biomarker tests to help predict who will get bladder cancer, discover the molecular profile of the disease to identify those most at risk, conduct a clinical trial testing green-tea extract and the experimental drug Iressa as prevention agents, and create a tumor bank to aid in scientific research.

The five-year effort is funded through a $5.9 million cancer-prevention grant from the National Cancer Institute (NCI) to the cancer center, the department of urology and the division of urologic oncology. This is the largest prevention study in the United States to focus on bladder cancer in current and former smokers, UCLA researchers said. While it is widely known that smoking causes lung cancer, tobacco use also is a major risk factor for bladder cancer, said Dr. Arie Belldegrun, a cancer researcher, chief of the division of urologic oncology, a professor of urology and principal investigator for the project.

“We will study innovative approaches to reduce the risk of bladder cancer,” Belldegrun said. “And while we’ll study prevention in patients who have already had bladder cancer, our goal is to develop effective prevention strategies for people who may be at risk but who do not yet have bladder cancer.”

This year, doctors will diagnose 56,500 cases of bladder cancer, most in men. In all, more than 12,600 people will die from bladder cancer. Most bladder cancer cases are smoking-related, said Dr. Robert Figlin, a Jonsson Cancer Center researcher, a professor of hematology/oncology and urology, and co-principal investigator for the study. Cigarette smokers are two to three times more likely than nonsmokers to get bladder cancer.

“What we’re doing is looking for things that tell us why some people get this disease and others don’t,” Figlin said. “We want to decrease bladder cancer occurrence and develop molecular profiles that tell us who is most at risk.”

Bladder cancer is a major health problem in the United States, ranking as the fourth most-common cancer in men and the eighth most-common in women, Belldegrun said.

“And cigarette smoking represents the single most significant, preventable cause of bladder cancer,” Belldegrun said.

The $5.9 million grant is part of the NCI’s chemoprevention program. Chemoprevention studies look at possible ways to prevent cancer with interventions that can include drugs, vitamins, diet, hormone therapy or other agents.

The Jonsson Cancer Center program will feature four angles of attack, bringing together physicians and scientists from different disciplines, including medicine, urology, epidemiology, biomathematics, biostatistics, pathology and surgery. The program includes:

· A clinical trial for 270 current and former smokers who have already had bladder cancer. The study, led by Dr. Allan Pantuck, an assistant professor of urology, will investigate the effectiveness of two compounds in preventing or delaying recurrence of the cancer and will divide volunteers into three arms. One group will receive green-tea extract, which has been shown in UCLA laboratories to reduce the growth of bladder cancer tumors both in animal models and in humans. The second group will receive an experimental drug called Iressa, an epidermal growth factor receptor inhibitor that also is being studied in lung and prostate cancers. The third group will receive a placebo.

· Development of a set of biomarkers for bladder cancer that can be used to predict who is likely to develop the disease. Such tests, to be developed by Drs. Zuo-Feng Zhang and Jian Yu Rao, could work similarly to the PSA test for prostate cancer.

· With Dr. Aarno Palotie of the UCLA Department of Human Genetics, discover a molecular profile of bladder cancer that will help determine susceptibility to the disease. Researchers will seek to uncover what specific genetic mutations and other abnormalities may put people at risk for bladder cancer, such as the BRCA1 and 2 genes do for breast cancer.

· Create a bladder cancer tumor bank for use by UCLA scientists from various medical and research disciplines for development of better prevention, detection and treatment methods for bladder cancer.

The bladder cancer-prevention program rounds out the Jonsson Cancer Center’s effort to better prevent and treat smoking-related cancers. UCLA researchers also are studying ways to prevent lung cancer. The popular anti-inflammatory drug Celebrex is being tested in people at high risk of developing the disease, which will kill more than 154,000 American men and women this year.

One Celebrex study involves lung cancer survivors who are at high risk of experiencing a recurrence or developing a new lung cancer. The other study involves individuals who smoke and are at high risk of developing lung cancer.

“This is an important effort for UCLA, examining ways to prevent these two smoking-related cancers,” Figlin said. “Together, these cancers strike more than 225,000 Americans every year, taking more than 167,000 lives.”

No one yet knows the causes of bladder cancer. Risk factors besides tobacco smoking include age, being a man (men are two to three times more likely to get bladder cancer than women), family history and race (whites are two to three times more likely to get bladder cancer than blacks, Latinos or Asians). There’s a 20-year latency period for smoking-related bladder cancer, UCLA researchers said, meaning it takes about 20 years for the cancer to develop in smokers and former smokers.

Symptoms of bladder cancer include blood in the urine, pain during urination and frequent urination or the need to urinate without results.

For more information on the UCLA bladder cancer-prevention study, or to volunteer for the clinical trial, please call (310) 794-7704.

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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