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New breakthrough discovered for lethal brain tumor

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Scientists at the School of Medicine have created an animal model of a rare and fatal brain tumor affecting young children. This model is the first of its kind and will allow scientists to better study Diffuse Intrinsic Pontine Glioma (DIGP), a disease that is fatal for nearly all children who are diagnosed, according to a paper published in the Proceedings of the National Academy of Sciences.

(ANASTASIA YEE/The Stanford Daily)

Led by pediatric neurologist Michelle Monje, the team found that these models could be made by injecting human DIGP cells, donated by the parents of deceased patients, directly into mice. Using this model, the team found new molecular signals that prompt the cancer to grow.

“In a mouse, that population of cells is responsive to the Hedgehog pathway, a signaling pathway important in normal development and many forms of cancer,” Monje said. “We tested the role [of the pathway] by regulating it genetically, and in mice with regulated pathways, […] cells didn’t look as strange.”

These signals could also one day hold the key to curing the cancer by acting as signals for anti-tumor drugs. Monje and her team said they planned to pursue potential cures.

The animal model represents some of the biggest advances for this particular disease, where treatment advances have been stagnant for 35 years, Monje said.

Part of the problem is the lack of available samples.

“The tumor is not biopsied, as diagnosis can be made radiologically (by MRI) and biopsy is dangerous because of the tumor location,”          wrote senior author Philip Beachy, professor of developmental biology, in an e-mail to The Daily.

Although Monje declined to give names, she said other research institutions have attempted to create samples as well. Stanford, however, is the first in the world to achieve any success.

DIPG is particularly difficult to treat because the cancerous cells entwine themselves with healthy cells in the brain stem. Since the brain stem is necessary for the body’s survival, surgery is not an option.

As a result, Monje’s findings “give a lot of hope,” said Danah Jewett, whose late son, Dylan, was one of the earliest donors to Monje’s research in January 2009.

“For 35 years, parents were told that their child was going to die,” Jewett said.

“These children need it so badly and their families need so badly,” she added.

DIPG, which primarily affects children ages five through nine, is one of the more common pediatric tumors, Monje said. It affects up to 400 children annually in the U.S. Less than 1 percent of victims live through the first five years once the cancer has set.

Six other families have followed in the Jewett’s footsteps and decided to donate their tumor cells, Monje said.

Her team has also been contacted by a number of other researchers interested in further studying the disease.

For their part, Beachy said that the team has two future studies lined up: the first on the new tumor model to determine what kinds of therapies might be useful, and another to understand the possible cell of origin and changes in normal cell function that cause the tumors.

Several pharmaceutical companies are also working to develop drugs that will treat this cancer. Monje’s new mouse models will test some of the drugs.

The research was funded in part by the National Institutes of Health, the National Brain Tumor Foundation and the Howard Hughes Medical Institute.

Ivy Nguyen contributed to this report.

 

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