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Potential brain cancer drug for children may damage bones
Date:3/10/2008

A novel drug that fully eliminated brain tumors from mice in a dramatic 2004 study has shown a darker sidecausing permanent bone damage in younger mice. The researcher who conducted both studies says the disappointing new finding raises concerns about using similar drugs to treat childrens cancers, at least until there is a more thorough understanding of possible risks.

Tom Curran, Ph.D., a developmental biologist at The Childrens Hospital of Philadelphia, led the study, published in the March 2008 issue of the journal Cancer Cell. The drug in question, HhAntag, is a signal transduction inhibitor--an agent that blocks signals along a biological pathway. In mice specially bred for these studies by Currans research group, HhAntag specifically acts against signals on a pathway leading to medulloblastoma, a type of brain tumor found mostly in children.

Much current cancer research has focused on signal transduction inhibitors (STIs) because of their potential to interrupt specific biological pathways that give rise to cancer. To date, only one STI has been approved by the Food and Drug Administration for use in children. That drug, which acts on different biological pathways than HhAntag does, has not been associated with any developmental defects in children. However, other STIs are currently in pediatric clinical trials.

His teams new findings, says Curran, raise a strong caution. While it is not clear that the bone defects we observed in mice would also occur in children, and while signal transduction inhibitors may still represent a highly promising approach to treating pediatric cancer, it may be important to perform preclinical testing in young animals before moving ahead to clinical trials, he added. Young animals could provide a model of a drugs potential effects during childhood development.

The drug used by Currans group acts on the hedgehog (Hh) pathway, which is known to play multiple roles during the development of m
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Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

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