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'Hedgehog' signal distinguishes lethal from localized prostate cancers

Johns Hopkins researchers have discovered a possible way to distinguish lethal metastatic prostate cancers from those restricted to the walnut-size organ.

If future studies show their test -- measuring the level of activity of a signaling pathway called Hedgehog -- can predict which prostate cancers will spread, the results could revolutionize decision making processes for prostate cancer patients, the researchers say.

Most prostate cancers grow slowly, making "watchful waiting" a common alternative to immediate surgical removal of the prostate. However, there's no sure-fire way to tell whose cancer will stay put in the gland, and whose will be aggressive and spread -- a development that despite aggressive treatment is usually fatal.

In the September 12 advance online edition of Nature, the Hopkins researchers report that only three of 12 localized prostate tumors obtained at surgery had detectable activity of the Hedgehog signaling pathway. In contrast, all 15 samples of metastatic prostate cancers, donated at patients' deaths, had Hedgehog activity, which was 10 to 100 times higher than the highest levels seen in localized tumors. It remains to be seen whether Hedgehog activity in localized cancers will predict the ability to be metastatic.

The Hedgehog pathway produces a well-known growth and development signal during embryonic and fetal stages. It is also active in some cancers, including prostate, pancreatic and stomach cancers and the brain tumor medulloblastoma, but the researchers' study is believed to provide the first evidence of its role in cancer's spread.

"If we can use Hedgehog activity to predict whether a tumor will metastasize, we will have a great diagnostic tool, but manipulating the Hedgehog signaling pathway may also offer a completely new way to treat metastatic prostate cancer," says David Berman, M.D., Ph.D., assistant professor of pathology, urology and oncology at Johns Hopkins. "Right now nothing
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
13-Sep-2004


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