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New possibilities for bladder cancer treatment

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A recent study, published in the journal Nature on Jan. 29, 2014, identified new potential therapeutic targets for a major form of bladder cancer. The results of this study provide important insights into the mechanisms underlying this disease.

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Bladder cancer causes over 200 deaths every year in Connecticut (over 15,000 deaths per year in the United States and approximately 150,000 deaths per year worldwide). Overall, the chance men will develop this cancer during their life is about 1 in 26. For women, the chance is about 1 in 90.

Treatment for this muscle-invasive bladder cancer has not advanced beyond surgery and chemotherapy or radiation. In the past 30 years, no new drugs have been approved for this disease. There are no recognized second-line therapies (second choices for treatments when the initial therapy does not work) and no approved targeted agents for this type of bladder cancer.

In this study, researchers examined bladder cancer that invades the muscle of the bladder, the deadliest form of bladder cancer. They discovered recurrent mutations in 32 genes. Many of these gene mutations have never been associated with bladder cancers before. In fact, 9 of these gene mutations were not previously known to be mutated in any type of cancer. These mutated genes (and pathways affected by these mutations) represent new potential therapeutic targets.

The researchers also found that genes that regulate chromatin (a combination of DNA and protein that determines how genes are expressed) were more frequently mutated in bladder cancer than in any other common cancer studied to date. Among the recurring mutations, the researchers also discovered frequent mutations in the HER2 gene. Because HER2 (which affects cell growth and development) is implicated in a significant portion of breast cancers, it is possible that new agents under development against breast cancer may also be effective in treating subsets of bladder cancer patients.

This project has dramatically improved our understanding of the molecular basis of bladder cancers and their relationship to other cancer types,” said lead author John Weinstein, M.D., Ph.D. from the University of Texas M.D. Anderson Cancer Center in Houston. “In the long run, the potential molecular targets identified may help us to personalize therapy based on the characteristics of each patient’s tumor.”

The real excitement about this project is that we now have a menu of treatment and research directions to pursue,” said Seth Lerner, M.D. from Baylor College of Medicine in Houston and another the senior authors of the paper. “The field is poised to use this information to make new advances toward therapies for a very-difficult-to-treat form of bladder cancer.”

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