Drug Identified That Inhibits the Growth of Aggressive Meningiomas

Drug Identified That Inhibits the Growth of Aggressive Meningiomas

Researchers have identified a drug that inhibits the growth of meningiomas, the most common type of primary intercranial tumor. Meningiomas are tumors that form in the meninges, for which treatment is surgery to remove the tumor and radiation therapy. Most meningiomas are benign and grow slowly, and the 5-year survival rate is 64% but around 20% of meningiomas are highly aggressive and can lead to disabilities and death.

While surgery and radiation therapy can be successful, if those treatments are not successful there are no further medical interventions for patients as there are no drugs that have been approved for treating the tumors. One of the problems with developing drugs to treat meningiomas has been the limited understanding of the biology of meningiomas.

Researchers at Northwestern Medicine, the University of California, San Francisco, and the University of Hong Kong used DNA methylation profiling on 656 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic, and single-cell approaches, and demonstrated that meningiomas consist of three molecular subgroups, each of which has distinct clinical outcomes, biological drivers, and therapeutic vulnerabilities.

By identifying these three DNA methylation groups, the researchers have been able to predict recurrence rates far more accurately than is possible using the current classification methods. They have also identified a drug that has been shown to inhibit the growth of most meningiomas.

Merlin-intact meningiomas, which account for 34% of all meningiomas, have the best outcomes and are susceptible to cytotoxic therapy. Immune-enriched meningiomas, which account for 38% of meningiomas, have intermediate outcomes, and hypermitotic meningiomas –28% of meningiomas – have the worst outcomes. This latter group is distinguished by convergent genetic and epigenetic mechanisms, which drive the cell cycle and are resistant to cytotoxic therapy.

The researchers found that aggressive meningiomas have several molecular changes in a cell division pathway, which allows them to divide more and return after surgery. The researchers identified a drug – abemaciclib – that blocks the cell division cycle, thus inhibiting tumor growth. The researchers demonstrated the effectiveness of the drug at inhibiting the growth of meningiomas in cell cultures, organoids, mouse models, and also used it for treating some patients in compassionate use cases, and their tumors decreased in size and symptoms eased, suggesting the drug could be used in clinical trials.

The researchers are now planning on making their molecular profiling generalizable to allow it to be offered to all patients with meningiomas to determine the likelihood of the tumor returning and to identify the patients who would benefit from treatment with the drug.

You can read more about the study in the paper – Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities – which was recently published in Nature Genetics. DOI: 10.1038/s41588-022-01061-8