Discovery of New Approach to Stop Cancer Cell Growth in Medulloblastoma

Medulloblastoma is a fast-growing tumor of the central nervous system that often spreads to other areas of the brain and spinal cord. This tumor mostly affects children, but it can also affect adults. The first phase in treating medulloblastoma is normally surgery, followed by radiation therapy and chemotherapy. Survival rates are about 70–80 percent if the disease does not spread. If the disease has spread, only 60% of people will survive.

Preclinical research in human tissue samples, human cell lines, and mice has revealed a new technique for starving tumor cells of energy to stop them from growing. If the results are replicated in human clinical trials, the current study may lead to improvements in how certain patients with medulloblastoma are handled in the future.

The study, led by scientists from Queen Mary University of London and sponsored by the charity Brain Tumor Research, was published in Nature Communications in a paper titled, “Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation.”

The researchers concluded that “deregulation of chromatin modifiers plays an important role in the pathogenesis of medulloblastoma, the most common malignant brain tumor in children.” “We found a BMI1-dependent susceptibility to inositol metabolism deregulation in a subset of medulloblastoma patients.”

Inositol hexaphosphate (IP6), a naturally occurring compound found in plants and animals, was chosen by the researchers. They showed that it prevents medulloblastoma and that it can be used in combination with chemotherapy to destroy tumor cells.

“Medulloblastoma is divided into four subgroups (WNT, SHH, G3, and G4),” said Silvia Marino, PhD, director of Queen Mary University of London's Brain Tumor Research Centre of Excellence and lead researcher. “Despite our and understanding of the molecular variations between these subgroups, the main treatment choices for all patients are surgery combined with radiotherapy and/or chemotherapy. To devise new, less toxic, targeted therapies, we urgently need to understand the main molecular events driving tumor growth in each subgroup.”

Despite being the most common and associated with a poor prognosis, G4 medulloblastoma is the least known of all subgroups. We discovered a novel mechanism by which this form of medulloblastoma can adapt its metabolism and develop out of control. We've also shown how this energy flow can be disrupted. These promising findings raise the prospect of developing new tailored therapies for children with this aggressive brain tumor.”

The development of medulloblastoma may be influenced by epigenetic changes. BMI1, a protein involved in this mechanism, is present in high concentrations in a variety of cancers, including brain tumors.

High levels of it are found in the G4 subgroup of medulloblastoma, where it promotes tumor development.

The researchers previously discovered that G4 medulloblastoma cells have high levels of BMI1, but they also lack a protein called CHD7. According to the current study, high levels of BMI1 enable cancer cells to change their metabolism and develop at a faster pace.

Researchers used inositol hexaphosphate to prevent the cells from metabolizing and growing too quickly (IP6). IP6 combined with chemotherapy improved the ability of IP6 to destroy tumor cells in mice, according to the researchers.

Hugh Adams, head of stakeholder relations at Brain Tumor Research, said, "It's fantastic news that gives us some much-needed optimism for the future." “There is still a long way to go, but we are hopeful that a clinical trial will be up and running soon.” Brain tumors kill more children and adults under the age of 40 than any other form of cancer, but just 1% of the national cancer budget has been dedicated to this deadly disease in the past. This is something that Brain Tumor Research is determined to change.”