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Targeted Therapies Offer Hope to Children with Brain Cancer

2016-11-01
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More than 4,000 children and teens are diagnosed with brain cancer each year, killing more children than any other cancer. Researchers at Huntsman Cancer Institute (HCI) at the University of Utah write in Cell Reports (“MEK Inhibitors Reverse Growth of Embryonal Brain Tumors Derived from Oligoneural Precursor Cells”) that they have identified an existing group of drugs that appear to reduce or eliminate a certain subgroup of childhood brain cancers while sparing normal brain tissue. The research was conducted using a new zebrafish animal model system developed by the researchers that closely resembles an aggressive subtype of pediatric brain tumors.


Medicilon boasts nearly 300 tumor evaluation models. At the same time, we are empowering innovative therapies to comprehensively evaluate and study immuno-oncology. We have completed model establishment and efficacy evaluation of immuno-therapies such as CAR-T, TCR-T, CAR-NK, oncolytic virus, antibody (monoclonal antibody, double antibody, polyclonal antibody, etc.), siRNA, AAV.

“For many pediatric brain tumors, no cell or animal model exists to test targeted, or personalized, medications that could significantly improve survival and alleviate the harmful side effects of conventional therapies,” explains Rodney Stewart, Ph.D., an assistant professor in the Department of Oncological Sciences at the University of Utah and an HCI investigator. “Indeed, children with rare brain tumors have few options for life-saving treatment. Our hope is by creating this animal model; we will be a step closer to finding effective therapies.”

    The researchers studied a particularly aggressive pediatric brain tumor, known as primitive neuroectodermal tumors of the central nervous system (CNS-PNET), for which few animal or cell line models exist. Stewart explained that treatments could not be tested without an animal model or cell lines. Over seven years, Dr. Stewart and his team worked to develop a model that, at the genomic level, closely modeled the human condition they hoped to study.

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“We spent a lot of time comparing brain tumors arising in fish with related human brain cancers at the molecular genetic level,” he says. “This is important because these childhood brain cancers are rare, and as a result, there are few patient samples to study for comparisons.”

    Human tissue samples were necessary, however, to construct a reliable model. “We needed to reach out to several groups,” Dr. Stewart explains, including Primary Children’s Hospital in Salt Lake City and The Hospital for Sick Children in Toronto. He credits discoveries announced by two other groups studying similar cancers that opened the way for his team to move forward. “They were able to reclassify CNS-PNET tumors into distinct subgroups at the molecular level. That opened up a new avenue for our team because that stratification enabled us to nail down what the zebrafish brain tumor model represents.”

    Using the model, Dr. Stewart’s lab tested already existing compounds to see if they could find a targeted therapy that would work on one of the newly identified subgroups—the oligo neural or NB_FOXR2 CNS-PNET subgroup. Through their work to create the tumor model, they knew that a particular drug already in human clinical trials might work.

    “When we treated the fish with MEK inhibitors, they exhibited a remarkable response,” says Dr. Stewart. “Not only was the tumor burden reduced, but it also eliminated the tumor in about 80% of the fish, and those tumors have not returned. This is a durable response from a transient treatment. It’s what we look for in cancer therapy, an effective drug that can be taken for a certain amount of time, but after the cancer is gone, patients can stop taking it and live their lives.”

    Dr. Stewart carefully emphasizes that while the brain tumor type between fish and humans is similar, more studies are needed to determine if the results can be translated into the clinic. He would like to see his discovery in the hands of physicians as soon as possible. “Currently, the outcome for children with these cancers is deplorable. We don’t want to wait much longer,” he says.

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