Drug takes new approach to fighting prostate cancer

June 17, 2013 | by Nicole White

Prostate cancer is the second-leading cause of cancer death among men in the United States, according to the American Cancer Society, and more than 29,000 will die of the disease this year alone.  A new City of Hope study suggests those numbers could ultimately be brought down.

lock and key Some prostate cancer drugs work on a lock-and-key principle, binding with androgen receptors before they can bind with androgens, as if they're blocking the locks from the keys. But a new cancer drug takes a different approach.

In findings being presented today at The Endocrine Society’s 95th annual meeting  in San Francisco, researchers say they’ve created a drug capable of inhibiting aggressive forms of prostate cancer that are resistant to standard drug treatments.

“Our novel prostate cancer drug works by a unique mechanism of action,” said Jeremy Jones, Ph.D.,  assistant professor in the Division of Molecular Pharmacology and lead author of the study. “Thus, it has the potential to treat cancers resistant to currently approved therapies.”

In a healthy prostate gland, cells express proteins known as androgen-receptors. These proteins are activated by androgens, male sex hormones that include testosterone. They also play an important role promoting the growth of prostate cancer cells.

Androgens and androgen-receptors fit together, like keys in locks. Current drug treatments work by preventing the hormones from binding to the androgen-receptor proteins. Some drugs compete with the hormones, sticking to the androgen-receptors before they can bind with the androgens (like blocking the locks from the keys). Others prevent androgens from being produced (like preventing keys from being manufactured). Specifically, these drugs block the androgens from attaching to a part of the receptors called the ligand-binding domain, part of the protein that hormones bind to when they activate the receptors.

By blocking all androgen activity, the drugs induce chemical castration.

In advanced prostate cancer, however, the cells can adapt and become resistant to the androgen blockage, or they can begin to multiply without androgens, allowing the cancer to spread. These aggressive prostate cancers are known as castration-resistant.

The drug examined in the new study, conducted in mice, is called pyrvinium pamoate. It  works by binding to a different part of the androgen-receptor, preventing it from being “switched on.” The drug doesn’t compete with the androgens and doesn't bind to the ligand-domain – the first potential prostate cancer drug to work this way.

Jones said the next steps for this research will include pinpointing exactly where the drug is binding on the androgen receptor, what other molecules are involved and how effective the drug is when given in small amounts.

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