Mifepristone, a drug used to induce abortions in the United States, may be an alternative treatment for the management of certain brain tumors, vestibular schwannomas, and for which few treatment options exist.
Researchers show in a new study that mifepristone, a drug long used to induce early abortions in the United States and Europe, would be a potential treatment of certain common brain tumors and difficult to treat: vestibular schwannomas.
Their results are published in Scientific Reports April 3, 2018.
Vestibular schwannoma
Schwannomas are tumors that generally occur in the context of type 2 neurofibromatosis, a genetic disease, and more rarely sporadically. Histologically, these tumors are not malignant, but they are dangerous when they grow in size because of their location at the base of the skull below the brain.
From cells of the Schwann sheath of the vestibular nerve, the balance nerve, these tumors can grow to the point of damaging the vestibular nerve and causing dizziness, but also neighboring structures with a risk of nerve paralysis. facial, hearing loss or even death if their development compresses the brainstem.
Currently, it is the 4th most common intracranial tumor. The only possible treatments are limited to surgical resection and radiotherapy. However, these two procedures expose patients to significant risks due to the difficulty of accessing the tumor, such as facial paralysis or hearing loss.
A solution resulting from IT screening
In order to find an alternative to these invasive treatments, the researchers carried out a computer screening of several drug databases. This consists in establishing, using an algorithm, a score of correspondence between known drugs and the genes expressed in a pathology for which there is no drug means.
They thus identified 8 drugs potentially capable of slowing or stopping the growth of vestibular schwannomas, including mifepristone. According to the researchers, mifepristone may help reduce or even avoid the need for surgery and radiation therapy.
What is mifepristone?
Mifepristone is a progesterone receptor and glucocorticoid antagonist used as a medicine to induce abortions before the 63rd day of amenorrhea.
This molecule is known for its antiproliferative effect on cervical, mammary, endometrial, ovarian and prostate cancer cells. In addition, it is a molecule which crosses the barrier between the blood and the brain (blood-brain barrier). This is why the researchers considered this treatment to be the best drug candidate.
Mifepristone, an FDA-approved drug, may halt the growth of vestibular schwannoma, a tumor associated with neurofibromatosis 2 (NF2) or occurring sporadically: https://t.co/N3jOaEqJvE @MassEyeAndEar #NIDCDgrantee pic.twitter.com/idkWR52RAo
– NIH NIDCD (@NIDCD) April 4, 2018
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 has very few side effects (mild fatigue, hot flashes, nausea, skin rashes).
The researchers conclude that mifepristone has significant therapeutic potential and hope to be able to begin a phase II clinical trial soon.
.
