A meningioma is a tumor that arises from the meninges. When meningioma recurs after surgery and radiation treatment, a patient is out of options. No drugs are approved for these aggressive tumors, which occur in up to 20% of cases and can lead to patient disability or even death. Now, scientists at Northwestern Medicine collaborated with scientists at the University of California, San Francisco, and the University of Hong Kong, and have discovered a drug that inhibits the growth of the most meningiomas in select patients, mouse models, organoids, and cell cultures.
Their findings are published in the journal Nature Genetics, in a paper titled, “Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities.”
“Meningiomas are the most common primary intracranial tumors,” the researchers wrote. “There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic, and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers, and therapeutic vulnerabilities.”
The drug is a newer cancer treatment called abemaciclib, and is a cell cycle inhibitor, meaning it blocks the cell division cycle and inhibits tumor growth.
The researchers discovered that meningiomas can be divided into molecular subgroups with different clinical outcomes and recurrence rates. Their method of classifying tumors allowed the scientists to predict recurrence more accurately than the current method of classifying the tumor.
“Our study identifies which patients we should treat with this drug because their tumor will likely respond to it,” said study leader and corresponding author, Stephen Magill, MD, PhD, an assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. “We now have the potential to give them options and hope for a longer, symptom-free life.”
“Eventually we hope to tailor medical therapy to the genetic changes within each individual person’s meningioma. We can find a weakness in that tumor, put a stick in the spokes, and stop it from growing,” Magill said.
“By doing that we found three separate groups of meningiomas based off their biology,” Magill said. “For each group, we found a different biological mechanism promoting the tumors’ growth, with each group having a different clinical outcome.”
These groups are different than the previous grading system and “are more accurate at predicting the clinical behavior of the tumor,” Magill said.
Scientists discovered that aggressive tumors have multiple molecular changes in a common pathway of cell division that enables the cells to divide more and come back after surgery.
“We wondered if by inhibiting that pathway we could stop the tumors from growing,” Magill said. “We tested that in multiple ways and found it was true in patients, mouse models, and cell cultures.”
Mice with meningiomas treated with the medication lived longer and their tumors didn’t grow as rapidly. The drug was also used off label as compassionate use in several patients whose tumors decreased in size and whose symptoms improved, suggesting the drug should be considered for clinical trials, Magill said.
The scientists plan to translate these findings and methods to make this molecular profiling generalizable and available to all patients with meningioma.
