Some cancer cells, however, have found a way to escape the normal death-promoting machinery the body has developed. These cells may suppress or even delete caspase 8, freeing themselves to become much more aggressive and survive in distant sites in the body.
"We've shown now in animals and human tissue that as soon as the neuroblastoma cells lose caspase 8, suddenly you have a much more aggressive disease," said Stupack. "This explains why we see the loss of caspase 8 in 70 percent of aggressive neuroblastomas in children."
Neuroblastoma is a solid tumor cancer that usually originates in the abdomen near the kidneys. In the majority of cases (about 70 percent), by the time of diagnosis the disease has already metastasized. The average age at diagnosis is two years old.
"It is clear this gene is a deciding factor in whether or not a cancer cell becomes metastatic, yet, surprisingly, it does not appear to be involved at all in the initial formation of the cancer," said Stupack. "As such, it is one of only a handful of true metastasis suppressor genes currently known."
A number of other cancers may use this same mechanism for regulating their metastatic properties, which the researchers are now studying. Caspase 8 loss or suppression is seen in about 70 percent of small cell lung cancer, about 10 percent of colon cancer and about 35 percent of medulloblastoma. While genetic mutation will sometimes delete both copies of the caspase 8 gene, typically the gene is simply silenced.
This paper opens up a new way of thinking about cancer therapy.
"Now we have a
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Contact: Nancy Stringer
healthscicomm@ucsd.edu
619-543-6163
University of California - San Diego
4-Jan-2006