Brain cancer: an old medicine offers a new alternative in schwannoma

Mifepristone, a drug used to induce abortions in the United States, may be a therapeutic alternative for the management of certain brain tumors, vestibular schwannomas, for which few treatment options exist.

Researchers show in a new study that mifepristone, a drug that has been used for a long time to cause early abortions in the United States and Europe, is a potential treatment for some common and difficult to treat brain tumors: vestibular schwannomas.

Their results are published in Scientific Reports on April 3, 2018.

Vestibular schwannoma

Schwannomas are tumors that usually occur in a context of neurofibromatosis type 2, a genetic disease, and more rarely sporadically. Histologically, these tumors are not malignant, but they are dangerous when they grow because of their location at the base of the skull under the brain.

Derived from the Schwann sheath cells of the vestibular nerve, the nerve of balance, these tumors can develop to the point of damaging the vestibular nerve and causing vertigo, but also nearby structures with a risk of nerve paralysis facial, hearing loss or even death if their development compresses the brainstem.

Currently, this is the 4th most common intracranial tumor. The only possible treatments are limited to surgical resection and radiotherapy. However, these two procedures expose the patients to significant risks because of the difficulty of access to the tumor, such as facial paralysis or loss of hearing.

A solution resulting from the computer screening

In order to find an alternative to these invasive treatments, the researchers conducted a computer screening of several drug databases. This consists of establishing, using an algorithm, a matching score between known drugs and the genes expressed in a pathology for which there is no medication.

They identified eight drugs potentially capable of slowing or stopping the growth of vestibular schwannomas, including mifepristone. According to the researchers, mifepristone could reduce or even eliminate the need for surgery and radiation therapy.

What is mifepristone?

Mifepristone is a progesterone receptor antagonist and glucocorticoid used as a drug to induce abortions before the 63rd day of amenorrhea.

This molecule is known for its antiproliferative effect on cervical, breast, endometrial, ovarian and prostate cancer cells. Moreover, it is a molecule that crosses the barrier between the blood and the brain (blood-brain barrier). This is why the researchers felt that this treatment was the best drug candidate.

Indeed, they found in their study that this molecule reduced the proliferation of tumor cells by 80%. A dose-dependent response was observed, along with a "dramatic" decrease in cell proliferation. In addition, mifepristone reduces the viability of cancer cells without affecting healthy cells, and induces very few adverse effects (mild fatigue, flushing, nausea, rash).

The researchers conclude that mifepristone has significant therapeutic potential and hope to soon begin a Phase II clinical trial.

Video: Skull Base Tumors (February 2020).