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Androgen receptor may explain male dominance in liver cancer
Date:5/19/2010

od, namely that men with HBV are much more likely to develop cancer than women with the same infection," said Aram Hezel, M.D., a gastrointestinal oncologist at the James P. Wilmot Cancer Center at University of Rochester Medical Center. "This is great use of the tools of genetics and mouse modeling to explain a clinical finding and most importantly turn our attention to potentially more promising treatment approaches for patients with hepatocellular carcinoma."

"This study also raises the possibility of prevention among men with HBV infection through inhibition of the androgen receptor," Hezel added. "The potential impact on clinical care is great."

For decades Chang has focused on the particular role of the AR in human health. In 1988 he successfully cloned AR, which led to breakthroughs in several AR-related diseases such as prostate and bladder cancer, and Kennedy's neuron disease, a rare and progressive motor disorder similar to Lou Gehrig's disease, and that affects only men.

The AR is central to the action of testosterone and has a profound effect on many organs. In previous experiments, Chang has shown that mice without AR have dramatically lower rates of bladder cancer, a cancer that strikes men three times more often than women.

Male dominance in liver cancer suggested that the AR would be a key factor, as well. (About 74 percent of liver cancer cases occur in men.) Chang's objective was to locate a new pathway for treatment that would not require depletion of androgen levels in the entire body, which amounts to castration and causes severe side effects for patients.

His study took the first step toward demonstrating this could be done, at least for early stage liver cancer. Researchers showed that an experimental drug, ASC-J9, attacked and degraded the faulty AR, and suppressed liver tumors in mice.

Chang developed ASC-J9 earlier this decade and first reported on its clinical potential in March 2007
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Contact: Leslie Orr
Leslie_Orr@urmc.rochester.edu
585-275-5774
University of Rochester Medical Center
Source:Eurekalert

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