Brain Tumor Gene Finding May Point Way to Precision Drug

Scientists at Harvard Medical School have spotted DNA mutations linked to a common brain tumor that more often affects women, in a study that may pave the way for treating the sometimes fatal disease with drugs targeting genes that spur its growth.

Using gene sequencing machines to scan the tumors that had been removed from 65 patients with meningioma, the researchers found nine with mutations in growth promoting genes that are targeted by cancer drugs already in testing or on the market. The findings, published this week in Nature Genetics, may offer hope to patients with meningioma tumors found in locations in the brain that make surgery risky or impossible.

“The wonderful thing about those mutations is that there are already drugs in the clinic to target cancers with those mutations,” said Rameen Beroukhim, an oncologist and cancer researcher at Boston-based Harvard Medical School and the Dana-Farber Cancer Institute who was senior author on the study, in a statement.

Each year about 18,000 Americans get meningioma, a tumor of the membrane lining of the brain, said Beroukhim, accounting for one third of brain tumors. Meningioma is twice as common in women, for reasons that aren’t fully clear, researchers said. While most cases can be cured with surgery, the disease can be fatal when it recurs or grows in locations where full surgical removal is impossible, such as near the skull base.

There are no approved drugs for the disease, Beroukhim said via telephone. “We very badly need new treatments,” for these patients, he said.

Mutations Identified

In the study, three of the meningioma tumors had mutations in a growth-driving gene called SMO. Meanwhile, six of the tumors had mutations another growth promoter called AKT1 or another related gene called MTOR.

SMO is targeted by the skin cancer drug Erivedge from Roche Holding AG, now approved for treating advanced basal cell carcinoma. Roche currently isn’t testing the basal cell cancer drug in meningioma but might consider doing so in the future, said Krysta Pellegrino, a spokeswoman for the company, which is based in Basel, Switzerland

“The data in the study are very interesting,” said Pellegrino in an e-mail.

Merck & Co. has an experimental drug for solid tumors called MK-2206 that blocks AKT in second stage trials. “It is premature to speculate” whether the company might test the compound in meningioma, said Caroline Lappetito, a spokeswoman for Whitehouse Station, New Jersey-based Merck.

The findings are the first to suggest that drugs already on laboratory shelves might help people with advanced cases of meningioma who have one of the newly identified mutations, said Beroukhim, who is also affiliated with the Broad Institute of MIT and Harvard.

“The hope is that patients with the mutations may respond to these drugs,” he said in a telephone interview. While patient trials of targeted drugs in meningioma could begin in a year, it is too early to know which drugs might be used in such trials, he said.

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