Metformin, a frequently given diabetic medication, has shown promise in laboratory trials against a rare kind of childhood brain tumor, according to an international team of researchers led by the University of Michigan Health Rogel Cancer Center.
Experts try various medicines to overcome different diseases. Though the contents are specific for the disease, in some experiments, they try to have such medicine to cure another disease. In a recent such experience, the medicine of diabetes is seen giving unexpected results to the patients of brain tumor especially those who have suffered from it since childhood.
How Diabetic Drugs Are Helping Treat A Rare Childhood Brain Tumor
Though experts have enough medicines that support improving the condition of the patient at different stages, this medicine is seen as more effective than many options that are particularly created for cancer.
Experiments that revealed new insights into group A posterior fossa ependymomas, or PFAs, led the study team to a possible new treatment strategy. According to Cancer.net data, the universally deadly tumors are a subgroup of ependymomas, which account for around 5% of pediatric brain malignancies and afflict roughly 240 children each year in the United States.
According to research lead author SriramVeneti, M.D., Ph.D., the Al and Robert Glick Family Research Professor of Pediatrics in the Department of Pathology at Michigan Medicine, “these sorts of cancers truly challenge our fundamental concept of cancer.”
Because most tumors are known to be caused by genetic mutations or mistakes, this is the case. Precision medicine aims to find these mutations and treat them with particular medications. However, the majority of PFAs do not have such cancer-causing genetic abnormalities.
“Back in 2016 that epigenetic alterations are actually the major drivers of these malignancies,” Venneti continued, referring to changes in how cells access and interpret DNA sequences rather than irreversible mutations in the DNA itself.
The University of Michigan researchers had previously established that a critical mutation in DIPGs alters cell metabolism, and they wondered if the overexpressed protein EZHIP did the same.
They discovered the solution through a meticulous set of studies in tumor cells and tissues, as well as magnetic resonance spectroscopic images of children performed in cooperation with Children’s Hospital Los Angeles.
PFAs rearrange the same two metabolic pathways previously linked to DIPGs, namely glycolysis and the mitochondrial tricarboxylic acid cycle. When seeking strategies to inhibit glucose metabolism—the same mechanism that causes PFA tumors—diabetes was a natural place to explore.
The researchers wanted to test how metformin, a popular diabetic medication, affected PFA tumor cells. Venneti says that it has increasingly been utilized in cancer clinical trials targeting tumor metabolism, not only because it has a proven safety record in adults and children but also because it has a proven safety record in adults and children.
“We tried it and discovered that metformin slowed the metabolism of cancer cells and killed them in certain PFA ependymoma tumors,” he added. “Unexpectedly, we discovered that metformin reduces EZHIP, the protein that caused the epigenetic alterations in the first place.”
The EZHIP protein causes the epigenetic alterations that produce malignant cancers, not mutations. As a result, there’s a really intriguing prospect of inhibiting the aberrant protein that’s actively generating these tumors therapeutically,” he says. Meanwhile, metformin reduced tumor metabolism, shrunk tumors, and led to extended survival periods in a subgroup of metformin-sensitive tumors when administered to mice bearing patient-derived tumors.
Panobinostat, a medication in clinical trials for various brain tumors, was able to overcome metformin resistance in one cell line, according to the researchers. The next stage, according to Venneti, will be to transfer the laboratory findings into a clinical study.
