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Embryonic pathway critical to growth of digestive tract tumors

A common signal critical for normal embryo development in many species also contributes to cancers of the esophagus, stomach and pancreas in people, according to Johns Hopkins researchers. Upwards of 50,000 cancer deaths a year may now be partly attributable to this pathway's activity, say the researchers. Their report appears in the Oct. 23 issue of Nature.

The signal, called Hedgehog, tells cells when and where to grow during embryonic development and is turned on in primitive cells, or stem cells, in adult tissues to trigger tissue repair. Researchers at Hopkins and elsewhere have already linked Hedgehog and its signaling pathway to a non-fatal skin cancer (basal cell carcinoma), a deadly lung cancer and the most common childhood brain cancer (medulloblastoma).

"Blocking this signal may one day help treat cancers for which there are currently few or no mechanism-based therapies," says senior author Philip Beachy, Ph.D., professor of molecular biology and genetics in Hopkins' Institute for Basic Biomedical Sciences and a Howard Hughes Medical Institute investigator. "For right now, the biggest question is whether it will pan out in people."

In experiments with cancer cell lines and tumor samples from patients, the scientists found that Hedgehog's signal is required for the cancers' growth. Moreover, a three-week course of a plant-derived chemical called cyclopamine, known to block Hedgehog, killed these cancers when grown in mice, causing no apparent harm to the animals.

"In mice, blocking the Hedgehog signal made the implanted tumors disappear," says the study's first author, David Berman, M.D., Ph.D., assistant professor of pathology at Hopkins. "It's been about three and a half months since we stopped the cyclopamine, and still the tumors haven't returned."

Unfortunately, cyclopamine is unlikely to be useful for patients because there just isn't enough of it, so the search is on to find Hedgehog blockers that could be m
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
22-Oct-2003


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