Nav: Home

Researchers identify possible approach to block medulloblastoma growth

October 24, 2019

CHAPEL HILL -- University of North Carolina Lineberger Comprehensive Cancer Center researchers have identified a potential approach to stop the growth of the most common type of brain tumor in children.

UNC Lineberger's Timothy Gerson, MD, PhD, and colleagues reported in the journal Development that by blocking a signal called GSK-3, they could control tumor growth in a subtype of medulloblastoma. Their preclinical findings may provide clues to a possible new targeted treatment strategy.

"This work could lead to new insights into developmental brain malformations and also to new treatments for medulloblastoma that may spare the severe side effects of radiation and typical chemotherapy," said Gerson, who is an associate professor in the UNC School of Medicine Department of Neurology.

While as many as 80 percent of children with medulloblastoma survive long-term with radiation and chemotherapy, researchers said there is a need to improve therapies in order to limit debilitating side effects from those treatments, as well as to develop treatments that work for children whose cancer don't respond to treatment.

"For one of the more common subtypes of medulloblastoma, we found we can target a signaling pathway to block tumor growth," said Jennifer Ocasio, PhD, the study's first author and a former graduate student in the UNC School of Medicine Neuroscience Curriculum. "By targeting this pathway, we think this would be a way to sidestep effects of radiation and chemotherapy that have a lot of side effects because we are blocking growth rather than killing these cells."

In laboratory studies using mice and cells, the researchers focused on a tumor subtype that accounts for about one-third of medulloblastoma cases. In this type of brain tumor, the Sonic Hedgehog cellular signal helps trigger a series of signals in developing brain cells that lead to an overgrowth of neurons in the cerebellum, which controls balance, speech and other activities.

When researchers used genetic engineering to remove GSK-3 before tumors form in laboratory models of medulloblastoma, they discovered upregulation of other signals, including an important one called WNT that instructed the cells that form tumors to stop dividing. The result was that by genetically inactivating GSK-3 in mice, they could prevent tumor growth. Then they tested a drug called CHIR98 that also blocks GSK-3, and found that it stops tumor cells from growing.

The researchers said their findings were surprising because other studies have shown that blocking GSK-3 actually stimulates growth in other parts of the brain. They cautioned while this treatment might be promising for a specific subtype of medulloblastoma, it could drive growth in other brain cancers, including other medulloblastoma subtypes.

"In other areas of the brain, parts of this signaling pathway are important to promoting growth," said Ocasio, who is now a postdoctoral fellow at St. Jude Children's Research Hospital. "We think this has to do with the cell types in medulloblastoma; progenitor cells are not exactly the same. These cells in the cerebellum have different regulators than cells in the forebrain, and they respond differently to the same signals."

Researchers have already begun work to evaluate this treatment type further in laboratory models. Ultimately, Gershon said their goal is to find therapies to increase survival rates for medulloblastoma, and to make therapy less toxic.

"While we can now allow most patients with medulloblastoma to survive long-term, almost everybody comes through treatment changed. Our goal would be to find ways to treat the disease that would provide fewer side effects," he said.
-end-
Ocasio received support from the National Institute of Neurological Disorders and Stroke. Gershon is supported by grants from the National Institute of Neurological Disorders and Stroke and the St. Baldrick's Foundation.

In addition to Gershon and Ocasio, other authors included Rolf Dale Bates and Carolyn D. Rapp.

UNC Lineberger Comprehensive Cancer Center

Related Chemotherapy Articles:

'Combo' nanoplatforms for chemotherapy
In a paper to be published in the forthcoming issue in NANO, researchers from Harbin Institute of Technology, China have systematically discussed the recent progresses, current challenges and future perspectives of smart graphene-based nanoplatforms for synergistic tumor therapy and bio-imaging.
Nanotechnology improves chemotherapy delivery
Michigan State University scientists have invented a new way to monitor chemotherapy concentrations, which is more effective in keeping patients' treatments within the crucial therapeutic window.
Novel anti-cancer nanomedicine for efficient chemotherapy
Researchers have developed a new anti-cancer nanomedicine for targeted cancer chemotherapy.
Ending needless chemotherapy for breast cancer
A diagnostic test developed at The University of Queensland might soon determine if a breast cancer patient requires chemotherapy or would receive no benefit from this gruelling treatment.
A homing beacon for chemotherapy drugs
Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy.
Chemotherapy or not?
Case Western Reserve University researchers and partners, including a collaborator at Cleveland Clinic, are pushing the boundaries of how 'smart' diagnostic-imaging machines identify cancers -- and uncovering clues outside the tumor to tell whether a patient will respond well to chemotherapy.
Researchers use radiomics to predict who will benefit from chemotherapy
Using data from computed tomography (CT) images, researchers may be able to predict which lung cancer patients will respond to chemotherapy, according to a new study.
How drugs can minimize the side effects of chemotherapy
Researchers at the University of Zurich have determined the three-dimensional structure of the receptor that causes nausea and vomiting as a result of cancer chemotherapy.
Capturing chemotherapy drugs before they can cause side effects
Although chemotherapy can kill cancer cells very effectively, healthy cells also suffer.
Tumors backfire on chemotherapy
Chemotherapy is an effective treatment for breast cancer, yet some patients develop metastasis in spite of it.
More Chemotherapy News and Chemotherapy Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Accessing Better Health
Essential health care is a right, not a privilege ... or is it? This hour, TED speakers explore how we can give everyone access to a healthier way of life, despite who you are or where you live. Guests include physician Raj Panjabi, former NYC health commissioner Mary Bassett, researcher Michael Hendryx, and neuroscientist Rachel Wurzman.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab