Loss of gene linked to spread of childhood cancer

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Scientists said on Wednesday that a gene which is usually missing in a common, aggressive childhood cancer suppresses the metastasis, or spread, of the disease to other parts of the body.

The finding, reported in the journal Nature, could lead to new treatments for neuroblastoma, a deadly cancer that occurs in children about 2 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 Dwayne Stupack, an assistant professor of pathology at the University of California, San Diego.

The gene called caspase 8 is missing in 70 percent of aggressive neuroblastomas in children.

Cancer develops when abnormal cells divide uncontrollably and form a tumour. The disease is more difficult to treat and more deadly if it spreads from its primary site to other areas in the body.

In the majority of children with neuroblastoma, by the time they are diagnosed the cancer has already spread.

“A major problem with cancer is not necessarily the primary tumour formation, but the ability of some tumour cells within that primary tumour to metastasise, or travel to distant sites, where they develop new tumours,” said David Cheresh, the senior author of the report.

The scientists showed that when neuroblastoma cells try to move away from the primary tumour, they encounter molecules which send out signals that activate caspase 8 which acts like a suicide gene. It tells the cells to destroy themselves because they are in foreign territory.

But some cancerous cells manage to bypass or delete caspase 8 which allows them to form tumours in other parts of the body.

Cheresh and his colleagues said the finding could apply to other cancers which may use the same mechanism to spread. Caspase 8 is missing or suppressed in about 70 percent of small cell lung cancer cases, 10 percent of colon cancers and 35 percent of medulloblastoma, a type of brain tumour.

“Now we have a road map for attacking not just the primary cancer but the metastatic cascade, the metastatic disease process,” said Cheresh.

“We now know the Achilles heel of the metastatic tumour cell. If we can develop drugs targeted at restoring caspase 8, we may be able to stop metastasis. That now appears feasible,” he added. 

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