Nav: Home

Reviving the protector: new tactic against medulloblastoma

June 11, 2018

Scientists have a new tactic with potential for fighting medulloblastoma, the most common and most aggressive form of brain tumor in children.

The results are scheduled for publication in Cancer Cell.

Several emerging anticancer treatments are called "epigenetic therapies," targeting the ways cancer cells shut off genes that could restrain their growth. The new tactic revives a protective gene called BAI1, by interfering with a protein that medulloblastoma cells use to silence BAI1.

Reactivating BAI1, with a compound that penetrates into the brain, blocks medulloblastoma growth in mice. Senior author Erwin Van Meir, PhD, says this compound could be a basis for drug discovery and a valuable tool for attacking other types of cancer as well.

"It was a surprise the molecule we identified was more specific than we thought." Van Meir says. "This opens up a new area in epigenetic therapy."

Van Meir says that the Cancer Cell paper brings together research in his lab over the last 10 years. His team had originally been studying BAI1, because it was silenced in glioblastoma, another malignant brain tumor seen in adults. They had initially noticed that BAI1 is a regulator of angiogenesis, the process by which tumors attract new blood vessels.

"It turns out this is not actually BAI1's most important function," Van Meir says.

BAI1 is also a "protector" of p53, which has a role in preventing many types of cancer by monitoring DNA damage and sensing other types of stress - p53 is sometimes called "guardian of the genome."

Senior research associate Dan Zhu, PhD, the first author of the paper, was able to work out how BAI1 (also known as ADGRB) protects p53: by holding back another protein, Mdm2, which tags p53 for degradation.

In mice, the interactions between BAI1 and other genes linked to brain tumors weren't clear until Van Meir and his colleagues started looking at models of medulloblastoma.

"Once we delved into medulloblastoma, it became very obvious," he says, adding that targeting BAI1 is likely to be effective across the four molecular sub-varieties of medulloblastoma.

The compound that reactivates the BAI1 gene, called KCC-07, was identified in collaboration with the lab of Bill Nelson at Johns Hopkins. It interferes with MBD2, a protein that binds methylated DNA. Methylation is generally a modification that shuts genes off, and some epigenetic therapies aim to inhibit methylation, such as azacytidine/Vidaza, used against myelodysplastic syndrome. However, inhibiting the process of methylation turns many genes on or off - targeting just one DNA-binding protein could be more specific, Van Meir says.

KCC-07 could inhibit medulloblastoma growth in cell culture and in mouse models, and "represents a promising chemical scaffold for further drug development," the researchers conclude.
-end-
The research was supported by the National Cancer Institute (CA086335, CA163722, CA138292), the National Institute of Neurological Disorders and Stroke (NS096236, NS055077), the CURE Childhood Cancer Foundation, the Southeastern Brain Tumor Foundation, St. Baldrick's Foundation and the Emory Pediatric Research Center.

Emory Health Sciences

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...