Treatment attacks brain tumor metabolism at several points.
A study published in Oncotarget that used gene therapy for glioblastoma showed promising results, potentially opening a door for future treatment options.
The study was prompted from years of close investigation of Emx2, a gene that inhibits the proliferation of astrocytes during embryonic growth.
“We know that during the early stages of development of the nervous system only neurons grow, whereas glial cells only start to proliferate when neuronal growth is practically complete,” said first study author Carmen Falcone. “In our previous studies we discovered that Emx2 is expressed at very high levels during the neuronal generation phase, whereas its action declines dramatically when the glial cells start to grow. So the gene keeps astrocyte growth in check up to a certain point.”
Since the tumors share many features with astroglia, researchers wanted to use this to their advantage. During the study, researchers started doing in vitro tests on cultures with various types of glioblastoma.
They found that in almost all of the samples, the tumor tissues collapsed in less than a week. Researchers first modeled in vitro the molecular mechanisms that intervene when the gene is switched on and the final effect.
The gene was shown to attack tumor metabolism at a minimum of 6 points, which researchers defined as very robust. Once the in vitro studies were completed, researchers started the first in vivo experiments on mice.
“So, to prevent damage to the healthy cells, neurons and astrocytes, we selected a specific ‘promotor,’ a piece of DNA that causes the therapeutic gene to become activated only in tumor cells, without attacking the other cells, and we replicated the same result as seen in the first in vitro tests,” the study authors wrote.
Researchers used the same mechanisms naturally adopted by viruses and introduced an active version of Emx2 into the tumor cells. The results of the study thus far has shown that Emx2 is able to kill cells of at least 4 different types of glioblastoma, both in vitro and in vivo in rodents, without damaging healthy cells.
Additionally, researchers observed that the treatment targeted numerous points of the tumor process, and could effectively contrast the development of aggressive recurrences.
“For these to form, there has to be a process of selection of the strongest tumor cells,” said researcher Antonello Mallamaci. “By targeting them at a variety of different points, we raise the standards in this selection process and -- hopefully -- we prevent the recurrences. Now we plan to extend the in vivo tests to other glioblastomas. With a lot of hard work and a bit of luck we hope that in a few years' time all this can translate into a tangible benefit for the unfortunate patients afflicted by this disease.”