Promising cancer drug may endanger child’s bones
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A compound that looked promising for treating a brain tumor found mostly in children may damage growing bone—possibly making it too dangerous to use in young patients, researchers reported on Monday.
The drug fully eradicated medulloblastoma tumors in mice in 2004. But further testing showed it caused permanent bone damage in immature mice, Tom Curran of The Children’s Hospital of Philadelphia and colleagues found.
Writing in the journal Cancer Cell, they said the drug, known by its experimental name HhAntag, will need to be developed with caution.
And, they said, similar drugs will need careful testing.
HhAntag, made by California-based Genentech, affects a gene called Hedgehog, involved in both normal development and in cancer.
It is a so-called signal transduction inhibitor, designed to interrupt Hedgehog’s cancer-causing effects.
Several such drugs are currently in pediatric clinical trials.
“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,” Curran said in a statement.
Medulloblastomas account for about one in five childhood brain tumors.
“Current therapy, involving a combination of surgery, radiation, and chemotherapy, is relatively successful with a five year survival rate of 78 percent,” Curran’s team wrote.
“However, the prognosis is much worse for patients younger than 3 and in older patients with metastatic disease.”
The Hedgehog-inhibiting drugs had been considered a promising new approach for these young patients.
But even brief use of the drug in 10- to 14-day-old mice caused permanent damage, Curran found.
“We already knew that the same biological pathway involved in the growth of tumors was also involved in bone development but we did not expect temporary inhibition to cause an irreversible change in bone growth,” Curran said.
It may be possible to find a way to protect the growing bones of children and still use the drug, Curran said.
“Thus, although the impact of a brief suppression of Hedgehog pathway on bone development in mice is quite striking, this should not preclude attempts to develop a highly promising anti-cancer treatment for pediatric medulloblastoma,” his team concluded.
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